Regulatory T cells limit induction of protective immunity and promote immune pathology following intestinal helminth infection

Sawant, Deepali V., Gravano, David M., Vogel, Peter, Giacomin, Paul, Artis, David, and Vignali, Dario A.A. (2014) Regulatory T cells limit induction of protective immunity and promote immune pathology following intestinal helminth infection. Journal of Immunology, 192 (6). pp. 2904-2912.

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Abstract

Foxp3+ regulatory T cells (Tregs) have a well-characterized role in limiting autoimmunity and dampening deleterious immune responses. However, a potential consequence of the immunosuppressive function of Tregs can be the limitation of protective immunity to infectious pathogens. Parasitic infections are a potent stimulus for the generation of Treg responses, which may be beneficial to both the parasite and the host by promoting persistence of infection and limiting immune-mediated pathology, respectively. In this study, we explore the functional role of Tregs post–low-dose infection with the intestinal helminth parasite Trichuris muris, which yields a chronic infection because of inefficient induction of Th2 responses. Early Treg depletion postinfection resulted in expedited worm clearance, and was associated with reduced Th1-mediated inflammation of the intestinal environment. Interestingly, this protective immunity was lost, and worm burden enhanced if Tregs were depleted later once the infection was established. Early and late Treg depletion resulted in enhanced Th2 and reduced Th1 cytokine and humoral responses. Blockade of the Th2 cytokine IL-4 resulted in a moderate increase in Th1 but had no effect on worm burden. Our findings suggest that Tregs preferentially limit Th2 cell expansion, which can impact infections where clear immune polarity has not been established. Thus, the impact of Treg depletion is context and time dependent, and can be beneficial to the host in situations where Th1 responses should be limited in favor of Th2 responses.

Item ID: 31512
Item Type: Article (Research - C1)
ISSN: 1550-6606
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Funders: National Institutes of Health (NIH), National Cancer Institute (NCI), American Lebanese Syrian Associated Charities, National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NIH Grant R01 AI091977, NCI Grant CA21765, NHMRC Overseas Biomedical Fellowship 613718
Date Deposited: 04 Jun 2014 05:43
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 70%
06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060502 Infectious Agents @ 15%
11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 15%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 60%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 40%
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