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6. |
- Blomberg, C, et al.
(author)
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Pattern of Accessory Regions and Invasive Disease Potential in Streptococcus pneumoniae.
- 2009
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 199, s. 1032-1042
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Journal article (peer-reviewed)abstract
- Background. The invasive disease potential (IDP) of Streptococcus pneumoniae differs between serotypes, but the reason for this is unknown. Methods. A total of 47 pneumococcal isolates from 13 serotypes with different IDPs in humans that belonged to 37 multilocus sequence types were compared by whole genome microarrays and mutant analyses. Results. Approximately 34% of the genes were variable, including 95 genes previously shown by signature-tagged mutagenesis (STM) to be required for invasive disease in mice. Many variable genes were localized to 41 accessory regions (ARs), of which 24 contained genes previously identified by STM as required for invasive disease. Only AR6 and AR34 were preferentially found in isolates of serotypes with high IDPs. Neither AR6, which carries a gene previously identified by STM as required for invasive disease and encodes a 6-phospho-beta glucosidase, nor the putative adhesin expressed by AR34 was required for mouse virulence in TIGR4. Conclusions. Pneumococci possess a repertoire of ARs that differ between clones and even between isolates of the same clone. The ARs required for invasive disease in humans may be redundant, as no unique pattern distinguished the most invasive clones from others. The ARs that contained genes previously identified by STM as required for virulence in mice were frequently absent from invasive human isolates. Only 1 AR (AR6) was present in almost all isolates from the serotypes with the highest IDP (1, 4, and 7F), whereas it was missing from many others.
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- Brown, Darron R., et al.
(author)
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The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Generally HPV-Naive Women Aged 16-26 Years
- 2009
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In: Journal Of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 199:7, s. 926-935
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Conference paper (peer-reviewed)abstract
- Background. Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated. Methods. We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotying was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of >= 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types. Results. Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31. Conclusions. HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for similar to 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type.
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9. |
- Cardell, Kristina, et al.
(author)
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Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine
- 2008
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 198:3, s. 299-304
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Journal article (peer-reviewed)abstract
- BACKGROUND: Hepatitis B vaccine has been shown to be highly efficient in preventing hepatitis B. However, 5%-10% of individuals fail to develop protective levels (>or=10 mIU/mL) of antibodies to hepatitis B surface antigen (anti-HBs) and are considered to be nonresponders. METHODS: A total of 48 nonresponders and 20 subjects naive to the HBV vaccine received a double dose of combined hepatitis A and B vaccine (Twinrix) at 0, 1, and 6 months. The levels of anti-HBs and antibodies to hepatitis A virus (anti-HAV) were determined before vaccination and 1 month after each dose. RESULTS: Among 44 nonresponders, protective anti-HBs levels were found in 26 (59%) after the first dose and in 42 (95%) after the third dose. Among the control subjects, the corresponding figures were 10% and 100%, respectively. All subjects seroconverted to anti-HAV. The titers of both anti-HBs and anti-HAV were lower in the previously nonresponsive subjects (P< .01). CONCLUSION: Revaccination of nonresponders to the standard hepatitis B vaccine regimen with a double dose of the combined hepatitis A and B vaccine was highly effective. This is most likely explained by the increased dose, a positive bystander effect conferred by the hepatitis A vaccine, or both.
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10. |
- Carlsson, Björn, et al.
(author)
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Simultaneous generation of cytomegalovirus-specific CD8+ and CD4+ T lymphocytes by use of dendritic cells comodified with pp65 mRNA and pp65 protein
- 2005
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 192:11, s. 1912-20
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Journal article (peer-reviewed)abstract
- Cytomegalovirus (CMV) disease remains a severe complication in patients who have undergone transplantation. Viremia can be prevented and treated by the adoptive transfer of donor-derived CMV-directed T cells. To ensure long-term protection against CMV disease, it is important to transfer CMV antigen-specific T cells that represent both the CD8+ and the CD4+ subsets. In the present study, we used as stimulators dendritic cells (DCs) that were electroporated with in vitro-transcribed 5'-capped polyadenylated messenger RNA (mRNA) that encoded the CMV pp65 protein (i.e., pp65 mRNA). These DCs could efficiently activate CMV-directed CD8+ T cells, as assayed by tetramer staining, interferon- gamma production, and cytolytic activity. We also used DCs that were pulsed with a recombinant pp65 protein to activate CMV-directed CD4+ T cells. When DCs were comodified with pp65 mRNA and pp65 protein, large numbers of CMV-directed CD8+ and CD4+ T cells were generated simultaneously. The approach outlined in the present study can be adapted for a clinical protocol that circumvents potential virus-related biohazards and is available to all patients independently of their human leukocyte antigen haplotype.
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15. |
- Edén, Arvid, 1975, et al.
(author)
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Immune activation of the central nervous system is still present after >4 years of effective highly active antiretroviral therapy.
- 2007
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In: The Journal of infectious diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 196:12, s. 1779-83
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Journal article (peer-reviewed)abstract
- Highly active antiretroviral therapy (HAART) effectively reduces human immunodeficiency virus (HIV) RNA in cerebrospinal fluid (CSF), as well as in plasma. The effect on intrathecal immunoactivation is less well studied. We had earlier found that a substantial number of patients still have evidence of intrathecal immunoactivation after up to 2 years of treatment. We identified 15 patients treated with HAART for > or =4 years who had plasma HIV-RNA levels of <50 copies/mL for > or =3.5 years. CSF samples were available from 10 patients before treatment. We measured white-blood-cell count, HIV-RNA level, neopterin level, and IgG index. During treatment, all patients had HIV-RNA levels of <50 copies/mL in plasma and CSF. In CSF, both neopterin level and IgG index decreased significantly. After 4 years, 9 (60%) of the 15 patients still had neopterin levels in CSF that were above the upper normal reference value (5.8 nmol/L). During HAART, 9 (60%) of the 15 patients had an abnormal IgG index (>0.63). HAART significantly decreases intrathecal immunoactivation, but, despite effective treatment for >4 years, with HIV-RNA levels <50 copies/mL for > or =3.5 years, a substantial proportion of patients continue to show signs of macrophage/microglia activation and intrathecal immunoglobulin production in the CNS.
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17. |
- Forslund, Ola, et al.
(author)
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Cutaneous human papillomaviruses found in sun-exposed skin: Beta-papillomavirus species 2 predominates in squamous cell carcinoma
- 2007
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 196, s. 876-83
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Journal article (peer-reviewed)abstract
- Background. A spectrum of cutaneous human papillomaviruses (HPVs) is detectable in nonmelanoma skin cancers, as well as in healthy skin, but the significance that the presence of these types of HPV DNA has for the pathogenesis of skin cancer remains unclear. Methods. We studied 349 nonimmunosuppressed patients with skin lesions (82 with squamous cell carcinomas, 126 with basal cell carcinomas, 49 with actinic keratoses, and 92 with benign lesions). After superficial skin had been removed by tape, paired biopsy samples-from the lesion and from healthy skin from the same patient-were tested for HPV DNA. Risk factors for HPV DNA were analyzed in multivariate models. Results. Overall, 12% of healthy skin samples were positive for HPV DNA, compared with 26% of benign lesions, 22% of actinic keratoses, 18% of basal cell carcinomas, and 26% of squamous cell carcinomas. HPV DNA was associated with sites extensively exposed to the sun, both for the lesions (odds ratio [OR], 4.45 [95% confidence interval {CI}, 2.44-8.111) and for the healthy skin samples (OR, 3.65 [95% CI 1.79-7.44]). HPV types of Beta-papillomavirus species 2 predominate in squamous cell carcinomas (OR, 4.40 [95% CI, 1.92-10.06]), whereas HPV types of Beta-papillomavirus species 1 are primarily found in benign lesions (OR, 3.47 [95% CI, 1.72-6.99]). Conclusions. Cutaneous HPV types are primarily detected at sites extensively exposed to the sun. HPV types of Beta-papillomavirus species 2, but not of species 1, are associated with squamous cell carcinoma.
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18. |
- Färnert, Anna, et al.
(author)
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Transmission-dependent tolerance to multiclonal Plasmodium falciparum infection
- 2009
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In: Journal of Infectious Diseases. - Chicago : University of Chicago Press. - 0022-1899 .- 1537-6613. ; 200:7, s. 1166-1175
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Journal article (peer-reviewed)abstract
- Whether the number of concurrent clones in asymptomatic Plasmodium falciparum infections reflects the degree of host protection was investigated in children living in areas with different levels of transmission on the coast of Kenya. The number of concurrent clones was determined on the basis of polymorphism in msp2, which encodes the vaccine candidate antigen merozoite surface protein 2. In a low-transmission area, most children had monoclonal infections, and diversity did not predict a risk of clinical malaria. In an area of moderate transmission, asymptomatic infections with 2 clones were, compared with 1 clone, associated with an increased risk of subsequent malaria. In a comparative assessment in a high-transmission area in Tanzania, multiclonal infections conferred a reduced risk. The different nonlinear associations between the number of clones and malaria morbidity suggest that levels of tolerance to multiclonal infections are transmission dependent as a result of cumulative exposure to antigenically diverse P. falciparum infections.
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19. |
- Gekara, Nelson O, et al.
(author)
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Signals triggered by a bacterial pore-forming toxin contribute to toll-like receptor redundancy in gram-positive bacterial recognition.
- 2009
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 199:1, s. 124-33
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Journal article (peer-reviewed)abstract
- The results illustrate that signals triggered by LLO contribute to TLR2 redundancy in recognition of L. monocytogenes. Under normal conditions, multiple and, sometimes, redundant pathways cooperate to induce a rapid antimicrobial defense. When one signaling pathway-in this case, TLR2-is removed from the system, the other pathways are still capable of mounting a sufficient response to ensure survival of the host.
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21. |
- Gisslén, Magnus, 1962, et al.
(author)
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Elevated cerebrospinal fluid neurofilament light protein concentrations predict the development of AIDS dementia complex.
- 2007
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In: The Journal of infectious diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 195:12, s. 1774-8
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Journal article (peer-reviewed)abstract
- The light subunit of neurofilament protein (NFL) is a sensitive indicator of central nervous system axonal injury. We retrospectively identified 9 subjects participating in a longitudinal cohort study who developed acquired immunodeficiency syndrome dementia complex (ADC) and who had had a lumbar puncture performed within 2 years before presentation. Elevated cerebrospinal fluid (CSF) NFL concentrations were found in 7 (78%) of the 9 case patients who later developed ADC, compared with 9 (33%) of 27 CD4 cell count-matched HIV-1-infected control subjects. By contrast, no differences were found in CSF HIV-1 RNA or neopterin concentrations between the 2 groups. CSF NFL may prove to be a useful predictive marker for ADC.
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24. |
- Henriques-Normark, B
(author)
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Pneumococcal serotypes and virulence - Reply
- 2006
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In: JOURNAL OF INFECTIOUS DISEASES. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 193:3, s. 477-478
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Journal article (other academic/artistic)
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26. |
- Jacobsen, Marc, et al.
(author)
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Ras-associated small GTPase 33A, a novel T cell factor, is down-regulated in patients with tuberculosis
- 2005
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In: Journal of Infectious Diseases. - Chicago, USA : University of Chicago Press. - 0022-1899 .- 1537-6613. ; 192:7, s. 1211-8
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Journal article (peer-reviewed)abstract
- Ras-associated small GTPases (Rabs) are specific regulators of intracellular vesicle trafficking. Interference with host cell vesicular transport is a hallmark of many intracellular pathogens, including the notable example Mycobacterium tuberculosis. We performed, by quantitative polymerase chain reaction, gene-expression analyses for selected Rab molecules in peripheral-blood mononuclear cells from patients with tuberculosis (TB) and healthy control subjects, to identify candidate genes that are critically involved in the host immune response. Comparison revealed significant differences in the expression of genes for Rab13, Rab24, and Rab33A. Rab33A gene expression was down-regulated in patients with TB and was predominantly expressed in CD8+ T cells. We excluded possible influences of differences in T cell percentages between the 2 study groups, demonstrating that Rab33A gene expression changes on the single-cell level. In vitro, Rab33A RNA expression was induced in T cells on activation and by dendritic cells infected with M. tuberculosis. Our findings identify Rab33A as a T cell regulatory molecule in TB and suggest its involvement in disease processes.
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27. |
- Kindberg, Elin, 1981-, et al.
(author)
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A deletion in the chemokine receptor 5 (CCR5) gene is associated with tickborne encephalitis
- 2008
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 197:2, s. 266-269
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Journal article (peer-reviewed)abstract
- Tickborne encephalitis (TBE) virus infections can be asymptomatic or cause moderate to severe injuries of the central nervous system. Why some individuals develop severe disease is unknown, but a role for host genetic factors has been suggested. To investigate whether chemokine receptor CCR5 is associated with TBE, CCR5Δ32 genotyping was performed among Lithuanian patients with TBE (n = 129) or with aseptic meningoencephalitis (n = 76) as well as among control subjects (n = 134). We found individuals homozygous for CCR5Δ32 (P = .026) only among patients with TBE and a higher allele prevalence among patients with TBE compared with the other groups studied. CCR5Δ32 allele prevalence also increased with the clinical severity of disease. © 2007 by the Infectious Diseases Society of America. All rights reserved.
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31. |
- Kristinsson, K G, et al.
(author)
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Effective treatment of experimental acute otitis media by application of volatile fluids into the ear canal
- 2005
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 191:11, s. 1876-1880
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Journal article (peer-reviewed)abstract
- Essential oils are volatile and can have good antimicrobial activity. We compared the effects of oil of basil ( Ocimum basilicum) and essential oil components ( thymol, carvacrol, and salicylaldehyde) to those of a placebo when placed in the ear canal of rats with experimental acute otitis media caused by pneumococci or Haemophilus influenzae. Progress was monitored by otomicroscopic examination and middle ear cultures. The treatment with oil of basil or essential oil components cured or healed 56%-81% of rats infected with H. influenzae and 6%-75% of rats infected with pneumococci, compared with 5.6%-6% of rats in the placebo group. Essential oils or their components placed in the ear canal can provide effective treatment of acute otitis media.
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32. |
- Larsson, Christer, 1975-, et al.
(author)
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Complications of pregnancy and transplacental transmission of relapsing-fever borreliosis
- 2006
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 194:10, s. 1367-1374
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Journal article (peer-reviewed)abstract
- Relapsing-fever borreliosis caused by Borrelia duttonii is a common cause of complications of pregnancy, miscarriage, and neonatal death in sub-Saharan Africa. We established a murine model of gestational relapsing fever infection for the study of the pathological development of these complications. We demonstrate that B. duttonii infection during pregnancy results in intrauterine growth retardation, as well as placental damage and inflammation, impaired fetal circulation, and decreased maternal hemoglobin levels. We show that spirochetes frequently cross the maternal-fetal barrier, resulting in congenital infection. Furthermore, we compared the severity of infection in pregnant and nonpregnant mice and show that pregnancy has a protective effect. This model closely parallels the consequences of human gestational infection, and our results provide insight into the mechanisms behind the complications of pregnancy that have been reported in human relapsing-fever infection.
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34. |
- Lundstedt, Ann-Charlotte, et al.
(author)
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Inherited susceptibility to acute pyelonephritis: a family study of urinary tract infection.
- 2007
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 195:8, s. 1227-1234
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Journal article (peer-reviewed)abstract
- Background. Urinary tract infections (UTIs) are important causes of morbidity and death. The present study investigated whether genetic factors influence susceptibility to acute pyelonephritis (APN). CXCR1 expression was investigated as a factor predisposing to APN, because low CXCR1 expression has been associated with disease susceptibility in mice and disease-prone children. Methods. The families of APN-prone children (n=130) and of age-matched control subjects without UTI (n=101) were studied. Three- generation pedigrees of UTI-associated morbidity were established by means of structured interviews of the families. CXCR1 expression was quantified by flow cytometric analysis of peripheral blood neutrophils obtained from family members and control subjects. Results. APN was significantly more common in the family members of the APN-prone children (20 [15%] of 130 family members) than in the relatives of the control subjects (3 [3%] of 101 family members) (P <.002). Acute cystitis, in contrast, occurred with equal frequency in both groups (19%; P=1.0). Some families included many affected individuals, consistent with a dominant pattern of inheritance, whereas other families showed a recessive pattern of disease susceptibility. CXCR1 expression was significantly lower in the APN-prone children and in their relatives than in pediatric and adult control subjects (P < .0001). Conclusions. Our results suggest that susceptibility to APN is inherited and that low CXCR1 expression might predispose to disease.
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35. |
- Margeridon-Thermet, S, et al.
(author)
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Ultra-deep pyrosequencing of hepatitis B virus quasispecies from nucleoside and nucleotide reverse-transcriptase inhibitor (NRTI)-treated patients and NRTI-naive patients
- 2009
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In: Journal of Infectious Diseases. - : University of Chicago Press. - 0022-1899 .- 1537-6613. ; 199:9, s. 1275-1285
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Journal article (peer-reviewed)abstract
- The dynamics of emerging nucleoside and nucleotide reverse-transcriptase inhibitor (NRTI) resistance in hepatitis B virus (HBV) are not well understood because standard dideoxynucleotide direct polymerase chain reaction (PCR) sequencing assays detect drug-resistance mutations only after they have become dominant. To obtain insight into NRTI resistance, we used a new sequencing technology to characterize the spectrum of low-prevalence NRTI-resistance mutations in HBV obtained from 20 plasma samples from 11 NRTI-treated patients and 17 plasma samples from 17 NRTI-naive patients, by using standard direct PCR sequencing and ultra-deep pyrosequencing (UDPS). UDPS detected drug-resistance mutations that were not detected by PCR in 10 samples from 5 NRTI-treated patients, including the lamivudine-resistance mutation V173L (in 5 samples), the entecavir-resistance mutations T184S (in 2 samples) and S202G (in 1 sample), the adefovir-resistance mutation N236T (in 1 sample), and the lamivudine and adefovir-resistance mutations V173L, L180M, A181T, and M204V (in 1 sample). G-to-A hypermutation mediated by the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like family of cytidine deaminases was estimated to be present in 0.6% of reverse-transcriptase genes. Genotype A coinfection was detected by UDPS in each of 3 patients in whom genotype G virus was detected by direct PCR sequencing. UDPS detected low-prevalence HBV variants with NRTI-resistance mutations, G-to-A hypermutation, and low-level dual genotype infection with a sensitivity not previously possible.
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37. |
- Modin Larsson, Malin, 1980-, et al.
(author)
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Antibody prevalence and titer to norovirus (genogroup II) correlate with secretor (FUT2) but not with ABO phenotype or Lewis (FUT3) genotype
- 2006
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In: J Infect Dis. - : Oxford University Press. ; 194:10, s. 1422-1427
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Journal article (peer-reviewed)abstract
- BACKGROUND: Histo-blood group antigens and secretor status have been associated with susceptibility to Norovirus infections, which suggests that antibody prevalence and titer might correlate with these phenotypes. METHODS: Plasma samples (n = 105) from Swedish blood donors that had been genotyped for secretor (FUT2) and Lewis (Le; FUT3) genotypes and phenotyped for ABO and Le blood groups were analyzed for immunoglobulin G antibody prevalence and titers to norovirus genogroup (GG) II.4. RESULTS: The results showed that nonsecretors (se4128se428) and Lea+b- individuals not only had significantly lower antibody titers than did secretors (P < .0001) and Lea-b+ individuals (P < .0002) but were also significantly more often antibody negative (P < .05). Antibody titers in secretors were not significantly different between individuals of different Le (FUT3) genotypes or different ABO phenotypes. CONCLUSIONS: Nonsecretors and Lea+b- individuals are significantly less prone to be infected with GGII noroviruses. This new information extends previous knowledge and supports the hypothesis that nonsecretors are relatively but not absolutely resistant to norovirus infections.
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39. |
- Mårtensson, Andreas, et al.
(author)
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Influence of consecutive-day blood sampling on polymerase chain reaction-adjusted parasitological cure rates in an antimalarial-drug trial conducted in Tanzania
- 2007
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In: Journal of Infectious Diseases. - Chicago : University of Chicago Press. - 0022-1899 .- 1537-6613. ; 195:4, s. 597-601
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Journal article (peer-reviewed)abstract
- We assessed the influence that consecutive-day blood sampling, compared with single-day blood sampling, had on polymerase chain reaction (PCR)-adjusted parasitological cure after stepwise genotyping of merozoite surface proteins 2 (msp2) and 1 (msp1) in 106 children in Tanzania who had uncomplicated falciparum malaria treated with either sulfadoxine-pyrimethamine or artemether-lumefantrine; 78 of these children developed recurrent parasitemia during the 42-day follow-up period. Initial msp2 genotyping identified 27 and 33 recrudescences by use of single- and consecutive-day sampling, respectively; in subsequent msp1 genotyping, 17 and 21 of these episodes, respectively, were still classified as recrudescences; these results indicate a similar sensitivity of the standard single-day PCR protocol--that is, 82% (27/33) and 81% (17/21), in both genotyping steps. Interpretation of PCR-adjusted results will significantly depend on methodology.
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41. |
- N'Guessan, PD., et al.
(author)
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The UspA1 protein of Moraxella catarrhalis induces CEACAM-1-dependent apoptosis in alveolar epithelial cells.
- 2007
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 195:11, s. 1651-1660
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Journal article (peer-reviewed)abstract
- Moraxella catarrhalis is a major cause of exacerbations of chronic obstructive pulmonary disease (COPD) and emphysema. M. catarrhalis–specific UspA1 and the epithelial carcinoembryonic antigen-related cell adhesion molecule (CEACAM1) were required to induce apoptosis. M. catarrhalis–induced apoptosis was significantly enhanced in HeLa cells stably transfected with CEACAM1, compared with HeLa cells not expressing CEACAM1. Infected cells showed increased activity of caspases 3, 6, and 9 but not of caspase 8. Reduced expression of Bcl-2, translocation of Bax into the mitochondria, and cytosolic increase of apoptosis-inducing factor in M. catarrhalis–infected cells implicated the involvement of mitochondrial death pathways. In conclusion, M. catarrhalis induced apoptosis in pulmonary epithelial cells—a process that was triggered by interaction between CEACAM1 and UspA1. Thus, M. catarrhalis–induced apoptosis of pulmonary epithelial cells may contribute to the development of COPD and emphysema.
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42. |
- Nowrouzian, Forough, 1957, et al.
(author)
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Escherichia coli strains belonging to phylogenetic group B2 have superior capacity to persist in the intestinal microflora of infants.
- 2005
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In: The Journal of infectious diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 191:7, s. 1078-83
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Journal article (peer-reviewed)abstract
- Escherichia coli strains segregate into 4 phylogenetic groups, designated "A," "B1," "B2," and "D." Pathogenic strains belong to group B2 and, to a lesser extent, group D, which more frequently carry virulence-factor genes than do group A strains and group B1 strains. This study investigated whether the capacity of E. coli to persist in the human intestine is related to its phylogenetic type. Resident (n=58) and transient (n=19) commensal E. coli strains isolated during a longitudinal study of 70 Swedish infants and previously tested for virulence-factor-gene carriage were tested for phylogenetic type. Of the strains resident in the intestinal microflora, 60% belonged to group B2, compared with only 21% of the transient strains (P=.004). In logistic regression, group B2 type predicted persistence in the intestinal microflora, independent of carriage of all investigated virulence-factor genes, including genes for P fimbriae (P=.03). Thus, group B2 strains appear to possess yet unidentified traits that enhance their survival in the human intestine.
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43. |
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44. |
- Pant, Neha, et al.
(author)
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Lactobacilli expressing variable domain of llama heavy-chain antibody fragments (lactobodies) confer protection against rotavirus-induced diarrhea
- 2006
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In: Journal of Infectious Diseases. - 0022-1899 .- 1537-6613. ; 194:11, s. 1580-1588
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Journal article (peer-reviewed)abstract
- Background. Rotavirus-induced diarrhea poses a worldwide medical problem in causing substantial morbidity and mortality among children in developing countries. We therefore developed a system for passive immunotherapy in which recombinant lactobacilli constitutively express neutralizing variable domain of llama heavy-chain (VHH) antibody fragments against rotavirus. Methods. VHH were expressed in Lactobacillus paracasei, in both secreted and cell surface-anchored forms. Electron microscopy was used to investigate the binding efficacy of VHH-expressing lactobacilli. To investigate the in vivo function of VHH-expressing lactobacilli, a mouse pup model of rotavirus infection was used. Results. Efficient binding of the VHH antibody fragments to rotavirus was shown by enzyme-linked immunosorbent assay and scanning electron microscopy. VHH fragments expressed by lactobacilli conferred a significant reduction in infection in cell cultures. When administered orally, lactobacilli-producing surface-expressed VHH markedly shortened disease duration, severity, and viral load in a mouse model of rotavirus-induced diarrhea when administered both fresh and in a freeze-dried form. Conclusions. Transformed lactobacilli may form the basis of a novel form of prophylactic treatment against rotavirus infections and other diarrheal diseases. © 2006 by the Infectious Diseases Society of America. All rights reserved.
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47. |
- Ragnarsdottir, Bryndis, et al.
(author)
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Reduced Toll-like receptor 4 expression in children with asymptomatic bacteriuria
- 2007
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 196:3, s. 475-484
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Journal article (peer-reviewed)abstract
- Toll-like receptor (TLR) 4 is essential for the defense against infection with gram-negative pathogens, but reduced TLR4 expression has not been linked to altered disease susceptibility in humans. In mice, Tlr4 controls the mucosal response to Escherichia coli urinary tract infections. Inactivation of mouse Tlr4 causes an asymptomatic carrier state resembling asymptomatic bacteriuria (ABU). The present study compared neutrophil TLR4 expression levels between children with ABU (n = 17) and age-matched control subjects (n = 24), and significantly lower levels were detected in the patients with ABU. We also found elevated levels of the TLR4 adaptor protein TRIF and reduced levels of the TLR4-inhibitor SIGIRR in the patients with ABU, but MyD88 and TRAM levels were not significantly altered. Altered TLR4 and adaptor protein expression might impair TLR4 signaling and explain the weak mucosal response to urinary tract infection in patients who develop ABU rather than symptomatic disease.
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- Ronander, Elena, et al.
(author)
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Nontypeable Haemophilus influenzae Adhesin Protein E: Characterization and Biological Activity.
- 2009
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 199, s. 522-531
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Journal article (peer-reviewed)abstract
- The adhesin protein E (PE) of the human respiratory pathogen nontypeable Haemophilus influenzae (NTHi) exists in all clinical isolates. In the present study, NTHi adherence to epithelial cells of various origins was further analyzed. The number of intraepithelial PE-deficient NTHi was decreased compared with PE-expressing NTHi. Interestingly, PE-expressing NTHi or Escherichia coli transformants, in addition to soluble recombinant PE22-160 without a lipid moiety, induced a proinflammatory cell response. The adhesive PE domain was defined within PE84-108, and preincubation of epithelial cells with this peptide blocked adhesion of several clinical NTHi isolates. Mice immunized with PE84-108 cleared NTHi up to 8-fold more efficiently on pulmonary challenge than did mice immunized with a control peptide. Finally, anti-PE mouse antibodies from vaccinated mice prevented NTHi adhesion. Our data suggest that the ubiquitous adhesin PE plays an important role in the pathogenesis of NTHi infection.
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