Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut

The Journal of Immunology : Official Journal of the American Association of Immunologists
Katja ObiegloSusanne Nylén

Abstract

Helminth infections have been suggested to impair the development and outcome of Th1 responses to vaccines and intracellular microorganisms. However, there are limited data regarding the ability of intestinal nematodes to modulate Th1 responses at sites distal to the gut. In this study, we have investigated the effect of the intestinal nematode Heligmosomoides polygyrus bakeri on Th1 responses to Mycobacterium bovis bacillus Calmette-Guérin (BCG). We found that H. polygyrus infection localized to the gut can mute BCG-specific CD4(+) T cell priming in both the spleen and skin-draining lymph nodes. Furthermore, H. polygyrus infection reduced the magnitude of delayed-type hypersensitivity (DTH) to PPD in the skin. Consequently, H. polygyrus-infected mice challenged with BCG had a higher mycobacterial load in the liver compared with worm-free mice. The excretory-secretory product from H. polygyrus (HES) was found to dampen IFN-γ production by mycobacteria-specific CD4(+) T cells. This inhibition was dependent on the TGF-βR signaling activity of HES, suggesting that TGF-β signaling plays a role in the impaired Th1 responses observed coinfection with worms. Similar to results with mycobacteria, H. polygyrus-infected mice displayed an...Continue Reading

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Citations

Feb 12, 2019·Parasite Immunology·Cajsa ClassonSusanne Nylén
Aug 10, 2017·Frontiers in Cellular and Infection Microbiology·Norus AhmedSusanne Hartmann
Jan 13, 2021·Proceedings of the National Academy of Sciences of the United States of America·Vanessa O EzenwaKaori Sakamoto
Jan 10, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Juliana Bernardi AggioAntonio Gigliotti Rothfuchs

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