| 1. |
- Wold, Agnes E, 1955, et al.
(författare)
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Breast feeding and the intestinal microflora of the infant--implications for protection against infectious diseases.
- 2000
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Ingår i: Advances in experimental medicine and biology. - Boston : Kluwer Academic Publishers. - 0065-2598. ; 478, s. 77-93
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Forskningsöversikt (refereegranskat)abstract
- Human breast milk contains an array of factors with anti-infectious potential, such as immunoglobulins (especially secretory IgA), oligosaccharides and glycoproteins with anti-adhesive capacity, and cytokines. Breast-feeding is associated with protection from the following infections or infection-related conditions: gastroenteritis, upper and lower respiratory tract infection, acute otitis media, urinary tract infection, neonatal septicaemia and necrotizing enterocolitis. Some of the protective effects may derive from an altered mucosal colonization pattern in the breast-fed infant. In other instances breast-fed infants develop less symptoms to the same microbe which causes disease in the bottle-fed infant. An example of an altered colonization pattern is that breast-fed infants have less P-fimbriated, but more type 1-fimbriated E. coli. This may protect against urinary tract infection in the breast-fed infant since P. fimbriae are the major virulence factor for urinary tract infection. An example of changed consequences of the same microbial colonization is that secretory IgA in the breast-milk protects very efficiently from translocation of intestinal bacteria across the gut mucosa by coating intestinal bacteria and blocking their interaction with the epithelium. This mechanism may protect the infant from septicaemia of gut origin and, possibly, necrotizing enterocolitis. Breast-milk is also highly anti-inflammatogenic and contains hormone like factors which counteract diarrhea. Thus, breast-fed infants may be colonized by recognized diarrheal pathogens and still remain healthy. Due to a less virulent intestinal microflora and decreased translocation breast-fed infants will obtain less stimuli for the gut immune system, resulting, in e.g., lower salivary IgA antibody titres.
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| 2. |
- Wennerås, Christine, 1963, et al.
(författare)
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Distinct Inflammatory Mediator Patterns Characterize Infectious and Sterile Systemic Inflammation in Febrile Neutropenic Hematology Patients
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Invasive infections and sterile tissue damage can both give rise to systemic inflammation with fever and production of inflammatory mediators. This makes it difficult to diagnose infections in patients who are already inflamed, e.g. due to cell and tissue damage. For example, fever in patients with hematological malignancies may depend on infection, lysis of malignant cells, and/or chemotherapy-induced mucosal damage. We hypothesized that it would be possible to distinguish patterns of inflammatory mediators characterizing infectious and non-infectious causes of inflammation, respectively. Analysis of a broad range of parameters using a multivariate method of pattern recognition was done for this purpose. Methods: In this prospective study, febrile (>38 degrees C) neutropenic patients (n = 42) with hematologic malignancies were classified as having or not having a microbiologically defined infection by an infectious disease specialist. In parallel, blood was analyzed for 116 biomarkers, and 23 clinical variables were recorded for each patient. Using O-PLS (orthogonal projection to latent structures), a model was constructed based on these 139 variables that could separate the infected from the non-infected patients. Non-discriminatory variables were discarded until a final model was reached. Finally, the capacity of this model to accurately classify a validation set of febrile neutropenic patients (n = 10) as infected or non-infected was tested. Results: A model that could segregate infected from non-infected patients was achieved based on discrete differences in the levels of 40 variables. These variables included acute phase proteins, cytokines, measures of coagulation, metabolism, organ stress and iron turn-over. The model correctly identified the infectious status of nine out of ten subsequently recruited febrile neutropenic hematology patients. Conclusions: It is possible to separate patients with infectious inflammation from those with sterile inflammation based on inflammatory mediator patterns. This strategy could be developed into a decision-making tool for diverse clinical applications.
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| 3. |
- Barman, Malin, 1983, et al.
(författare)
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Cord Blood Levels of EPA, a Marker of Fish Intake, Correlate with Infants' T- and B-Lymphocyte Phenotypes and Risk for Allergic Disease
- 2020
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 12:10, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- Maternal fish intake during pregnancy has been associated with reduced allergy development in the offspring and here, we hypothesized that components of fish stimulate fetal immune maturation. The aim of this study was to investigate how maternal fish intake during pregnancy and levels of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in the infant's cord serum correlated with different subsets of B- and T-cells in cord blood and B-cell activating factor (BAFF) in cord plasma, and with doctor-diagnosed allergy at 3 and 8 years of age in the FARMFLORA birth-cohort consisting of 65 families. Principal component analysis showed that infant allergies at 3 or 8 years of age were negatively associated with the proportions of n-3 LCPUFAs (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) in infant cord serum, which, in turn correlated positively with maternal fish intake during pregnancy. Both maternal fish intake and cord serum n-3 LCPUFAs correlated negatively to CD5(+) B cells and the FOXP3(+)CD25(high) of the CD4(+) T cell subsets in cord blood, but not to BAFF in cord plasma. Our observational study suggests that fish might contain components that promote maturation of the infant's immune system in a manner that protects against allergy development.
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| 4. |
- Carlsson, Johan, 1987, et al.
(författare)
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The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro : AA and DHA Induce DCs That Suppress T Cells
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naive T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 muM fatty acids; alpha-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNgamma. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells.
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| 5. |
- Carlsson, Johan, 1987, et al.
(författare)
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The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 10:11, s. e0143741-
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Tidskriftsartikel (refereegranskat)abstract
- Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naive T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 muM fatty acids; alpha-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNgamma. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells.
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| 6. |
- Mölne, Johan, 1958, et al.
(författare)
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Inflammation
- 2007
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Boken behandlar på ett lättfattligt sätt alla typer av inflammationssjukdomar. Den är avsedd för studenter på läkar- biolog- och apotekarlinjer, men kan läsas av alla med intresse för biologi och medicin. Den är rikt illustrerad av författarna
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| 7. |
- Barkman, Cecilia, 1962, et al.
(författare)
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Soluble bacterial constituents down-regulate secretion of IL-12 in response to intact Gram-positive bacteria.
- 2008
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Ingår i: Microbes and infection / Institut Pasteur. - : Elsevier BV. - 1286-4579. ; 10:14-15, s. 1484-93
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Tidskriftsartikel (refereegranskat)abstract
- Intact Gram-positive bacteria induce production of large amounts of IL-12 from freshly isolated human monocytes. Here the bacterial structures and signalling pathways involved were studied and compared with those leading to IL-6 production, and to IL-12 production in response to LPS after IFN-gamma pre-treatment. Intact bifidobacteria induced massive production of IL-12 (1ng/ml) and IL-6 (>30ng/ml) from human PBMC, whereas fragmented bifidobacteria induced IL-6, but no IL-12. IL-12 production induced by intact bifidobacteria was inhibited by pre-treatment with bifidobacterial sonicate, peptidoglycan, muramyl dipeptide, lipoteichoic acid, the soluble TLR2 agonist Pam(3)Cys-SK(4), or anti-TLR2 antibodies. Blocking of phagocytosis by cytochalasin, inhibition of the JNK or NF-kappaB pathways or treatment with Wortmannin also reduced the IL-12 response to intact Gram-positive bacteria. LPS induced moderate levels of IL-12 (0.31ng/ml), but only from IFN-gamma pre-treated PBMC. This IL-12 production was enhanced by Wortmannin and unaffected by blocking the JNK pathway. Thus, intact Gram-positive bacteria trigger monocyte production of large amounts of IL-12 via a distinct pathway that is turned off by fragmented Gram-positive bacteria. This may be a physiological feedback, since such fragments may signal that further activation of the phagocyte via the IL-12/IFN-gamma loop is unnecessary.
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| 8. |
- Dahlgren, Ulf, 1953, et al.
(författare)
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Expression of a dietary protein in E. coli renders it strongly antigenic to gut lymphoid tissue.
- 1991
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Ingår i: Immunology. - 0019-2805. ; 73:4, s. 394-7
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Tidskriftsartikel (refereegranskat)abstract
- Bacteria that colonize the intestinal mucosa elicit a strong mucosal immune response, whereas food antigens such as ovalbumin are very weakly immunogenic to the gut-associated lymphoid tissue. This may either be due to special physico-chemical properties of bacterial substances versus proteins from animals and plants, or to stimulating properties of the bacteria on, e.g., antigen presentation, rendering all substances contained within bacteria antigenic. To test these hypotheses, ovalbumin was expressed in wild-type Escherichia coli and germ-free female rats were colonized with this strain. The systemic and mucosal antibody response of these rats was compared with that of rats given large amounts of dietary ovalbumin. Biliary IgA antibodies, which reflect the local IgA antibody production in the intestine, were only found in the rats colonized with ovalbumin-synthesizing E. coli. IgG antibodies in the bile were also only seen in these rats. We conclude that mucosal immunogenicity depends on the context in which a protein is presented to the gut-associated lymphoid tissue, rather than to special antigenic characteristics of the protein in itself.
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| 9. |
- Gio-Batta, Monica, et al.
(författare)
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Low Concentration of Fecal Valeric Acid at 1 Year of Age Is Linked with Eczema and Food Allergy at 13 Years of Age : Findings from a Swedish Birth Cohort
- 2022
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger. - 1018-2438 .- 1423-0097. ; , s. 398-408
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Tidskriftsartikel (refereegranskat)abstract
- Background: Short-chain fatty acids (SCFAs) are abundant bacterial metabolites in the gut, with immunomodulatory properties. Hence, they may influence allergy development. Previous studies have linked fecal SCFA pattern during infancy with allergy. However, the association of SCFAs to allergic outcomes in adolescence is not well established. Here, we examined how the fecal SCFA pattern at 1 year of age related to allergy at 13 years of age.Methods: Levels of 8 SCFAs in fecal samples collected at 1 year of age from 110 children were quantified using gas chromatography. The same individuals were evaluated at 13 years of age for allergic symptoms, allergy diagnosis and allergy medication by questionnaire, and for sensitization using skin prick test against egg, milk, fish, wheat and soy, cat, dog, horse, birch, and timothy grass.Results: The concentration of fecal valeric acid at 1 year of age was inversely associated with eczema at 13 years of age (OR 0.6, 95% CI: 0.4-1.0, p = 0.049) and showed a trend for inverse association with food allergy at 13 years of age (OR 0.6, 95% CI: 0.4-1.0, p = 0.057). In a sub-group analysis of children with eczema at 1 year of age, a higher concentration of fecal valeric acid was linked with reduced risk of their eczema remaining at 13 years of age (OR 0.2, 95% CI: 0.0-1.5), although this latter analysis did not reach statistical significance (p = 0.12).Conclusions: Our findings lend further support to the notion of early childhood as a critical period when allergy may be programmed via the gut microbiota. Higher levels of fecal valeric acid may be characteristic of a protective gut microbiota and/or actively contribute to protection from eczema and food allergy.
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| 10. |
- Herías, M V, et al.
(författare)
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Immunomodulatory effects of Lactobacillus plantarum colonizing the intestine of gnotobiotic rats.
- 1999
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 116:2, s. 283-90
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the effect of the probiotic strain Lactobacillus plantarum 299v on the immune functions of gnotobiotic rats. One group of germ-free rats was colonized with the type 1-fimbriated Escherichia coli O6:K13:H1 and another group with the same E. coli strain together with L. plantarum 299v. One and 5 weeks after colonization, bacterial numbers were determined in the contents of the small intestine, caecum and mesenteric lymph nodes. Small intestinal sections were examined for CD8+, CD4+, CD25+ (IL-2R alpha-chain), IgA+ and MHC class II+ cells and mitogen-induced spleen cell proliferation was determined. Immunoglobulin levels and E. coli-specific antibodies were measured in serum. Rats given L. plantarum in addition to E. coli showed lower counts of E. coli in the small intestine and caecum 1 week after colonization compared with the group colonized with E. coli alone, but similar levels after 5 weeks. Rats colonized with L. plantarum + E. coli had significantly higher total serum IgA levels and marginally higher IgM and IgA antibody levels against E. coli than those colonized with E. coli alone. They also showed a significantly increased density of CD25+ cells in the lamina propria and displayed a decreased proliferative spleen cell response after stimulation with concanavalin A or E. coli 1 week after colonization. The results indicate that L. plantarum colonization competes with E. coli for intestinal colonization and can influence intestinal and systemic immunity.
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