Human Cellular Immune Response Against Giardia lamblia 5 Years After Acute Giardiasis

Hanevik, Kurt; Kristoffersen, E. K.; Svärd, Staffan G.; Bruserud, Øystein; Ringqvist, Emma; Sørnes, Steinar; Langeland, Nina

doi:10.1093/infdis/jir639

Cited by 36 publications

(31 citation statements)

References 38 publications

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“…Increased levels of T cell markers specific for Giardia-exposed individuals have been shown before (22). Also in the present study, CD45RO/HLA-DR CD4 T cell responses were shown to be significantly elevated in SSA-and SSB-stimulated cells.…”

Section: Discussionsupporting

confidence: 82%

“…IFN-␥ was se-creted, and cells were found to be proliferating in response to trophozoites, suggesting that Giardia-specific proliferation of CD4 ϩ T cells exists in humans as well (21). CD4 ϩ T cell memory immune responses in peripheral blood mononuclear cells (PBMCs) from humans were investigated 5 years after a large outbreak of Giardia occurred (22). Giardia-specific CD4 ϩ T cell responses were found to be present by the upregulation of surface activation markers (CD25/CD26 and CD45RO/HLA-DR) and higher proliferation rates of T cells in Giardia-exposed persons compared to those in controls.…”

Section: Decreased or Nonexistent Cd4mentioning

confidence: 99%

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Human Memory CD4 ⁺ T Cell Immune Responses against Giardia lamblia

Saghaug

Sørnes

Peirasmaki

et al. 2016

Clin Vaccine Immunol

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؉ EM T cells, as well as that of cells simultaneously producing both IL-17A and TNF-␣, 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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Section: Discussionsupporting

confidence: 82%

Section: Decreased or Nonexistent Cd4mentioning

confidence: 99%

Human Memory CD4 ⁺ T Cell Immune Responses against Giardia lamblia

Saghaug

Sørnes

Peirasmaki

et al. 2016

Clin Vaccine Immunol

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“…The relative abundances of T cell populations within the IEL, however, are unaltered throughout infection in our model. The proliferation of Giardia-specific CD4 ϩ T cells has been reported in mice and humans (37)(38)(39). Several studies have shown that CD4 ϩ T cells are necessary for clearance of Giardia infections, and recent data have suggested that interleukin-17 (IL-17) is a key cytokine in mediating this protective effect (reviewed in reference 40).…”

Section: Infection With G Duodenalis Results In Increased Cd4mentioning

confidence: 99%

The Microbiota Contributes to CD8⁺T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis

Keselman

Maloney

et al. 2016

Infect Immun

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Giardia duodenalis is a noninvasive luminal pathogen that impairs digestive function in its host in part by reducing intestinal disaccharidase activity. This enzyme deficiency has been shown in mice to require CD8 ؉ T cells. We recently showed that both host immune responses and parasite strain affected disaccharidase levels during murine giardiasis. However, high doses of antibiotics were used to facilitate infections in that study, and we therefore decided to systematically examine the effects of antibiotic use on pathogenesis and immune responses in the mouse model of giardiasis. We found that antibiotic treatment did not overtly increase the parasite burden but significantly limited the disaccharidase deficiency observed in infected mice. Moreover, while infected mice had more activated CD8 ؉ ␣␤ T cells in the small intestinal lamina propria, this increase was absent in antibiotictreated mice. Infection also led to increased numbers of CD4 ؉ ␣␤ T cells in the lamina propria and activation of T cell receptor ␥␦-expressing intraepithelial lymphocytes (IEL), but these changes were not affected by antibiotics. Finally, we show that activated CD8؉ T cells express gamma interferon (IFN-␥) and granzymes but that granzymes are not required for sucrase deficiency. We conclude that CD8؉ T cells become activated in giardiasis through an antibiotic-sensitive process and contribute to reduced sucrase activity. These are the first data directly demonstrating activation of CD8؉ T cells and ␥␦ T cells during Giardia infections. These data also demonstrate that disruption of the intestinal microbiota by antibiotic treatment prevents pathological CD8 ؉ T cell activation in giardiasis.T he protozoan Giardia duodenalis is a major cause of parasitic diarrheal disease worldwide. Infection with G. duodenalis provides an interesting model for studying mucosal immunity, as some of the immunopathology observed in human patients and infected animals resembles that of common noninfectious intestinal disorders. The reduction of intestinal disaccharidase enzymes, for example, is a pathological hallmark of giardiasis and is also commonly observed in gastroenteritis, celiac disease, ulcerative colitis, and Crohn's disease patients (1-4). Therefore, there are likely overlapping mechanisms involved. The reduction of disaccharidase enzymes in giardiasis results from a shortening of the intestinal epithelial microvilli structures and reflects a general impairment of digestion and nutrient absorption (5-7). We have demonstrated that wild-type mice exhibit reduced disaccharidase activity following infection with G. duodenalis but that CD4Another study has demonstrated that the adoptive transfer of purified CD8 ϩ T cells, but not CD4 ϩ T cells, from Giardia muris-infected mice into athymic naive recipients is sufficient to recapitulate shortening of microvilli and intestinal disaccharidase reduction (7). Collectively, these data suggest that CD8 ϩ T cells are involved in the pathological reduction of intestinal disaccharidases following infection...

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“…In severe cases of giardiasis, during infection Giardia trophozoites attach to the epithelium of the proximal small bowel aided by their ventral adhesive discs, evade host defenses possibly by undergoing genetic variation (12), and produce local alterations of villus structure and cellular apoptosis. The most devastating effects of Giardia infection are related to damage of the absorptive small bowel mucosa, together with abnormal intestinal immunity that favors chronic infection (13,14). While there is little evidence that preexistent malnutrition in young children makes them more susceptible to Giardia infection, once they are infected, persistent symptoms and health consequences are more likely to develop (15).…”

Section: Discussionmentioning

confidence: 99%

Giardia: both a harmless commensal and a devastating pathogen

DuPont

2013

J. Clin. Invest.

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Human Cellular Immune Response Against Giardia lamblia 5 Years After Acute Giardiasis

Abstract: 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.

Cited by 36 publications

References 38 publications

Human Memory CD4 ⁺ T Cell Immune Responses against Giardia lamblia

Human Memory CD4 ⁺ T Cell Immune Responses against Giardia lamblia

The Microbiota Contributes to CD8⁺T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis

Giardia: both a harmless commensal and a devastating pathogen

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Human Cellular Immune Response Against Giardia lamblia 5 Years After Acute Giardiasis

Abstract: 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.

Cited by 36 publications

References 38 publications

Human Memory CD4 + T Cell Immune Responses against Giardia lamblia

Human Memory CD4 + T Cell Immune Responses against Giardia lamblia

The Microbiota Contributes to CD8+T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis

Giardia: both a harmless commensal and a devastating pathogen

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Human Memory CD4 ⁺ T Cell Immune Responses against Giardia lamblia

Human Memory CD4 ⁺ T Cell Immune Responses against Giardia lamblia

The Microbiota Contributes to CD8⁺T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis