Human Memory CD4
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            T Cell Immune Responses against Giardia lamblia

Saghaug, Christina Skår; Sørnes, Steinar; Peirasmaki, Dimitra; Svärd, Staffan G.; Langeland, Nina; Hanevik, Kurt

doi:10.1128/cvi.00419-15

Cited by 56 publications

(51 citation statements)

References 38 publications

(52 reference statements)

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“…The IL-17A mRNA level is elevated in the guts of cattle and mice infected with Giardia, and mice lacking IL-17A exhibit a severe defect in controlling infections with either Giardia muris or G. duodenalis (43)(44)(45). Moreover, IL-17A memory T cell responses correlated with more rapid elimination of infections in a cohort of travelers with giardiasis (46). Our data show that IL-17A responses are significantly reduced in the absence of signaling via C3aR.…”

Section: Discussionmentioning

confidence: 49%

Complement Activation by Giardia duodenalis Parasites through the Lectin Pathway Contributes to Mast Cell Responses and Parasite Control

Tako

Singer

2016

Infect Immun

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Infection with Giardia duodenalis is one of the most common causes of diarrheal disease in the world. While numerous studies have identified important contributions of adaptive immune responses to parasite control, much less work has examined innate immunity and its connections to the adaptive response during this infection. We explored the role of complement in immunity to Giardia using mice deficient in mannose-binding lectin (Mbl2) or complement factor 3a receptor (C3aR). Both strains exhibited delayed clearance of parasites and a reduced ability to recruit mast cells in the intestinal submucosa. C3aR-deficient mice had normal production of antiparasite IgA, but ex vivo T cell recall responses were impaired. These data suggest that complement is a key factor in the innate recognition of Giardia and that recruitment of mast cells and activation of T cell immunity through C3a are important for parasite control. Giardia duodenalis is one of the most common protozoan infections of humans as well as other mammals throughout the world and is a leading cause of diarrheal disease in these species (1-3). Symptomatic infections occur in ϳ20 to 80% of humans with positive stool samples and are characterized by nausea, vomiting, epigastric pains, and diarrhea (1, 2, 4, 5). These symptoms are associated with nutrient malabsorption and can lead to weight loss and malnutrition in children, exposing this vulnerable group to failure to thrive and developmental problems (6, 7). Disease resolves spontaneously in Ͼ85% of cases. In certain cases, in spite of a healthy and fully developed immune system, the acute phase of the disease develops into chronic disease. In these cases, symptoms of the disease will reappear for short and recurrent periods (3,4,8). The mechanisms explaining interactions between the host and the parasite leading to parasite clearance and disease pathogenesis are poorly understood.Studies of immune responses against Giardia have demonstrated important roles for both innate and adaptive immunity (7, 9). Antibody production following infection is robust, and IgA is very effective at eliminating parasites (9). Antibody-independent roles of T cells can also eliminate infections (10). Early studies indicated that Giardia trophozoites are susceptible to killing by factors in nonimmune human serum, milk, and intestinal fluid (11-13). Recently, killing by normal serum was demonstrated to involve the lectin pathway (14), consistent with the expression of N-acetylglucosamine (GlcNAc) on the surface of trophozoites (15,16). Studies of cells of the innate immune system indicate that macrophages, dendritic cells, mast cells, and intestinal epithelial cells are all involved. In vitro macrophages have been shown to be capable of ingesting Giardia, and we recently showed that macrophages accumulate in the lamina propria following infection (17, 18). Bone marrow-derived dendritic cells mature in response to Giardia extracts, but cytokine production in response to Toll-like receptor (TLR) agonists is modulated toward interle...

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Section: Discussionmentioning

confidence: 49%

Complement Activation by Giardia duodenalis Parasites through the Lectin Pathway Contributes to Mast Cell Responses and Parasite Control

Tako

Singer

2016

Infect Immun

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“…Li et al [88] found a reduction in IL-17 responses in the absence of signaling via C3aR, which suggest that a decrease in mast cell recruitment also correlates with decreased IL-17 production. In human patients that have recovered from Giardia , IL-17 has been found to be upregulated when effector memory CD4 + T-cell are restimulated with Giardia antigen [89]; in addition, several studies [25, 87, 90, 91] reported the upregulation of IL-17 during murine or bovine infections, and delayed parasite clearance in IL-17 knockout mice has also been reported [87, 90]. Moving forward it will be interesting to understand the effector mechanisms triggered by IL-17 and the signaling mechanisms leading to activation of IL-17 production during giardiasis.…”

Section: Protective Immunity Towards Giardiamentioning

confidence: 99%

The Intersection of Immune Responses, Microbiota, and Pathogenesis in Giardiasis

Fink

Singer

2017

Trends in Parasitology

104

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Giardia lamblia is one of the most common infectious protozoans in the world. Giardia rarely causes severe life-threatening diarrhea, and may even have a slight protective effect in this regard, but it is a major contributor to malnutrition and growth faltering in children in the developing world. Giardia infection also appears to be a significant risk factor for post-infectious irritable bowel and chronic fatigue syndromes. In this review we highlight recent work focused on the impact of giardiasis and the mechanisms that contribute to the various outcomes of this infection, including changes in the composition of the microbiota, activation of immune responses, and immunopathology.

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“…Giardia lamblia elicits both a cellular and humoral immune response, inducing cytokines such as tumour necrosis factor (TNF), interferon (IFN)‐y and interleukin (IL)‐17, as well as nitric oxide (NO), production of antigiardial IgA antibodies and intestinal mastocytosis . The relationship between giardiasis and allergy has been considered in the context of food allergy and allergic skin diseases .…”

Section: Protozoa and Allergy In Brazilmentioning

confidence: 99%

Parasites and allergy: Observations from Brazil

Andrade

Carneiro

Cerqueira

et al. 2018

Parasite Immunology

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Brazil is a middle-income country undergoing the epidemiological transition. Effects of changes in daily life habits and access to clean water, sanitation and urban services on a growing urban population have contributed to a double burden of both infectious and noncommunicable chronic diseases. Studies have indicated that parasite infections may modulate the human immune system and influence the development of allergic conditions such as asthma. However, there is no consensus in the published literature on the effects of parasitic infections on allergy, perhaps as a consequence of factors determining the epidemiology of these infections that vary between populations such as age of first infection, duration and chronicity of infections, parasite burden and species, and host genetic susceptibility. In this review, we discuss the observations from Brazil concerning the relationship between parasite infections and allergy.

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Human Memory CD4 ⁺ T Cell Immune Responses against Giardia lamblia

Cited by 56 publications

References 38 publications

Complement Activation by Giardia duodenalis Parasites through the Lectin Pathway Contributes to Mast Cell Responses and Parasite Control

Complement Activation by Giardia duodenalis Parasites through the Lectin Pathway Contributes to Mast Cell Responses and Parasite Control

The Intersection of Immune Responses, Microbiota, and Pathogenesis in Giardiasis

Parasites and allergy: Observations from Brazil

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Human Memory CD4 + T Cell Immune Responses against Giardia lamblia

Cited by 56 publications

References 38 publications

Complement Activation by Giardia duodenalis Parasites through the Lectin Pathway Contributes to Mast Cell Responses and Parasite Control

Complement Activation by Giardia duodenalis Parasites through the Lectin Pathway Contributes to Mast Cell Responses and Parasite Control

The Intersection of Immune Responses, Microbiota, and Pathogenesis in Giardiasis

Parasites and allergy: Observations from Brazil

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Human Memory CD4 ⁺ T Cell Immune Responses against Giardia lamblia