| 1. |
- Hanevik, Kurt, et al.
(author)
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Giardia-specific cellular immune responses in post-giardiasis chronic fatigue syndrome
- 2017
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In: BMC Immunology. - : BIOMED CENTRAL LTD. - 1471-2172. ; 18
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Journal article (peer-reviewed)abstract
- Background: The role of pathogen specific cellular immune responses against the eliciting pathogen in development of post-infectious chronic fatigue syndrome (PI-CFS) is not known and such studies are difficult to perform. The aim of this study was to evaluate specific anti-Giardia cellular immunity in cases that developed CFS after Giardia infection compared to cases that recovered well. Patients reporting chronic fatigue in a questionnaire study three years after a Giardia outbreak were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for CFS and idiopathic chronic fatigue. Giardia specific immune responses were evaluated in 39 of these patients by proliferation assay, T cell activation and cytokine release analysis. 20 Giardia exposed non-fatigued individuals and 10 healthy unexposed individuals were recruited as controls. Results: Patients were clinically classified into CFS (n = 15), idiopathic chronic fatigue (n = 5), fatigue from other causes (n = 9) and recovered from fatigue (n = 10). There were statistically significant antigen specific differences between these Giardia exposed groups and unexposed controls. However, we did not find differences between the Giardia exposed fatigue classification groups with regard to CD4 T cell activation, proliferation or cytokine levels in 6 days cultured PBMCs. Interestingly, sCD40L was increased in patients with PI-CFS and other persons with fatigue after Giardia infection compared to the non-fatigued group, and correlated well with fatigue levels at the time of sampling. Conclusion: Our data show antigen specific cellular immune responses in the groups previously exposed to Giardia and increased sCD40L in fatigued patients.
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| 2. |
- Hanevik, Kurt, et al.
(author)
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Human Cellular Immune Response Against Giardia lamblia 5 Years After Acute Giardiasis
- 2011
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 204:11, s. 1779-1786
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Journal article (peer-reviewed)abstract
- Background. Clinical and epidemiological studies have suggested the development of acquired immunity in individuals previously infected with Giardia lamblia. However, there are no data on the long-term cellular immunity and genotype cross-reactivity. An outbreak of assemblage B giardiasis in a nonendemic area made it possible to evaluate the long-term cellular mediated immunity and its specificity toward the 2 Giardia assemblages known to infect humans. Methods. Peripheral blood mononuclear cells from 19 individuals infected with Giardia assemblage B 5 years previously and from 10 uninfected controls were cultured with antigens from assemblage A and B Giardia trophozoites for 6 days. Cell-mediated immunity was measured by a (3)H-thymidine proliferation assay and flow cytometric analysis of activation markers HLA-DR, CD45RO, CD25, and CD26 in T-cell subsets. Results. Proliferation responses were significantly elevated in the group previously exposed to Giardia for nearly all Giardia antigens tested. Individual responses toward Giardia trophozoite whole cell, cytosolic, and excretory-secretory antigens from both assemblages correlated well. Activation marker responses were mainly seen in CD4 T cells. Conclusions. G. lamblia infection induces long-term, albeit variable, cellular immune responses that are not assemblage specific and that are largely driven by CD4 T-cell activation.
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| 3. |
- Saghaug, Christina Skar, et al.
(author)
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Human Memory CD4+ T Cell Immune Responses against Giardia lamblia
- 2016
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In: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 23:1, s. 11-18
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Journal article (peer-reviewed)abstract
- The intestinal protozoan parasite Giardia lamblia may cause severe prolonged diarrheal disease or pass unnoticed as an asymptomatic infection. T cells seem to play an important role in the immune response to Giardia infection, and memory responses may last years. Recently, T(H)17 responses have been found in three animal studies of Giardia infection. The aim of this study was to characterize the human CD4+ T cell responses to Giardia. Peripheral blood mononuclear cells (PBMCs) were obtained from 21 returning travelers with recent or ongoing giardiasis and 12 low-risk healthy controls and stimulated in vitro with Giardia lamblia proteins. Production of tumor necrosis factor alpha (TNF-alpha), gamma interferon, interleukin-17A (IL-17A), IL-10, and IL-4 was measured in CD4+ effector memory (EM) T cells after 24 h by flow cytometry. After 6 days of culture, activation and proliferation were measured by flow cytometry, while an array of inflammatory cytokine levels in supernatants were measured with multiplex assays. We found the number of IL-17A-producing CD4+ EM T cells, as well as that of cells simultaneously producing both IL-17A and TNF-alpha, to be significantly elevated in the Giardia-exposed individuals after 24 h of antigen stimulation. In supernatants of PBMCs stimulated with Giardia antigens for 6 days, we found inflammation-associated cytokines, including 1L-17A, as well as CD4+ T cell activation and proliferation, to be significantly elevated in the Giardia-exposed individuals. We conclude that symptomatic Giardia infection in humans induces a CD4+ EM T cell response of which IL-17A production seems to be an important component.
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