title: Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut.
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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors.forename: Katja
authors.initials: K
authors.lastname: Obieglo
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors.forename: Vishnu Priya
authors.initials: VP
authors.lastname: Bollampalli
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors.forename: Isabel
authors.initials: I
authors.lastname: Dellacasa-Lindberg
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors.forename: Cajsa
authors.initials: C
authors.lastname: Classon
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors.forename: Markus
authors.initials: M
authors.lastname: Österblad
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and.
authors.forename: Helena
authors.initials: H
authors.lastname: Helmby
authors.affiliation: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.
authors.forename: James P
authors.initials: JP
authors.lastname: Hewitson
authors.affiliation: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Maizels
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; Susanne.Nylen@ki.se Antonio.Rothfuchs@ki.se.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gigliotti Rothfuchs
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; Susanne.Nylen@ki.se Antonio.Rothfuchs@ki.se.
authors.forename: Susanne
authors.initials: S
authors.lastname: Nylén
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002908:Chronic Disease; D060085:Coinfection; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005767:Gastrointestinal Diseases / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology / Q000473:pathology; D006790:Host-Parasite Interactions / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009164:Mycobacterium Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D009163:Mycobacterium bovis / Q000276:immunology; D009349:Nematode Infections / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D000947:Antigens, Helminth; D011948:Receptors, Antigen, T-Cell; D018125:Receptors, Transforming Growth Factor beta
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