Chronic gastrointestinal nematode infection mutes immune responses to mycobacterial infection distal to the gut

Obieglo, K. et al. (2016) Chronic gastrointestinal nematode infection mutes immune responses to mycobacterial infection distal to the gut. Journal of Immunology, 196(5), pp. 2262-2271. (doi: 10.4049/jimmunol.1500970) (PMID:26819205) (PMCID:PMC4760231)

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 increase in skin parasite load upon secondary infection with Leishmania major as well as a reduction in DTH responses to Leishmania Ag. We show that a nematode confined to the gut can mute T cell responses to mycobacteria and impair control of secondary infections distal to the gut. The ability of intestinal helminths to reduce DTH responses may have clinical implications for the use of skin test–based diagnosis of microbial infections.

• Item Type: Articles
• Additional Information: This work was supported by the Swedish Research Council, the Bill and Melinda Gates Foundation Grand Challenge Award, Åke Wibergs Stiftelse, Stiftelsen Claes Groschinskys Minne, Karolinska Institutet funds, European Union/Marie Curíe Grant FP7-MC-IRG-247684, and the Swedish Society for Medicine.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maizels, Professor Rick
• Authors: Obieglo, K., Feng, X., Bollampalli, V. P., Dellacasa-Lindberg, I., Classon, C., Osterblad, M., Helmby, H., Hewitson, J. P., Maizels, R. M., Gigliotti Rothfuchs, A., and Nylen, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Immunology
• Publisher: American Association of Immunologists
• ISSN: 0022-1767
• ISSN (Online): 1550-6606
• Published Online: 27 January 2016