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

Katja Obieglo; Xiaogang Feng; Vishnu Priya Bollampalli; Isabel Dellacasa-Lindberg; Cajsa Classon; Markus Österblad; Helena Helmby; James P Hewitson; Rick M Maizels; Antonio Gigliotti Rothfuchs; Susanne Nylén

doi:10.4049/jimmunol.1500970

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

Katja Obieglo, Xiaogang Feng, Vishnu Priya Bollampalli, Isabel Dellacasa-Lindberg, Cajsa Classon, Markus Österblad, Helena Helmby, James P Hewitson, Rick M Maizels, Antonio Gigliotti Rothfuchs, Susanne Nylén

Centre for Immunology and Infection

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	2262-2271
Number of pages	10
Journal	Journal of Immunology
Volume	196
Issue number	5
DOIs	https://doi.org/10.4049/jimmunol.1500970
Publication status	E-pub ahead of print - 27 Jan 2016

Keywords

Animals
Antigens, Bacterial
Antigens, Helminth
Cell Movement
Chronic Disease
Coinfection
Dendritic Cells
Disease Models, Animal
Disease Susceptibility
Gastrointestinal Diseases
Host-Parasite Interactions
Host-Pathogen Interactions
Lymphocyte Activation
Mice
Mice, Knockout
Mycobacterium Infections
Mycobacterium bovis
Nematode Infections
Receptors, Antigen, T-Cell
Receptors, Transforming Growth Factor beta
Signal Transduction
T-Cell Antigen Receptor Specificity
T-Lymphocyte Subsets

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10.4049/jimmunol.1500970

Cite this

Obieglo, K., Feng, X., Bollampalli, V. P., Dellacasa-Lindberg, I., Classon, C., Österblad, M., Helmby, H., Hewitson, J. P., Maizels, R. M., Gigliotti Rothfuchs, A., & Nylén, S. (2016). Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut. Journal of Immunology, 196(5), 2262-2271. Advance online publication. https://doi.org/10.4049/jimmunol.1500970

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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-Gu{\'e}rin (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.",

keywords = "Animals, Antigens, Bacterial, Antigens, Helminth, Cell Movement, Chronic Disease, Coinfection, Dendritic Cells, Disease Models, Animal, Disease Susceptibility, Gastrointestinal Diseases, Host-Parasite Interactions, Host-Pathogen Interactions, Lymphocyte Activation, Mice, Mice, Knockout, Mycobacterium Infections, Mycobacterium bovis, Nematode Infections, Receptors, Antigen, T-Cell, Receptors, Transforming Growth Factor beta, Signal Transduction, T-Cell Antigen Receptor Specificity, T-Lymphocyte Subsets",

author = "Katja Obieglo and Xiaogang Feng and Bollampalli, {Vishnu Priya} and Isabel Dellacasa-Lindberg and Cajsa Classon and Markus {\"O}sterblad and Helena Helmby and Hewitson, {James P} and Maizels, {Rick M} and {Gigliotti Rothfuchs}, Antonio and Susanne Nyl{\'e}n",

note = "Copyright {\textcopyright} 2016 by The American Association of Immunologists, Inc.",

year = "2016",

month = jan,

day = "27",

doi = "10.4049/jimmunol.1500970",

language = "English",

volume = "196",

pages = "2262--2271",

journal = "Journal of Immunology",

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publisher = "American Association of Immunologists",

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Obieglo, K, Feng, X, Bollampalli, VP, Dellacasa-Lindberg, I, Classon, C, Österblad, M, Helmby, H, Hewitson, JP, Maizels, RM, Gigliotti Rothfuchs, A & Nylén, S 2016, 'Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut', Journal of Immunology, vol. 196, no. 5, pp. 2262-2271. https://doi.org/10.4049/jimmunol.1500970

TY - JOUR

T1 - Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut

AU - Obieglo, Katja

AU - Feng, Xiaogang

AU - Bollampalli, Vishnu Priya

AU - Dellacasa-Lindberg, Isabel

AU - Classon, Cajsa

AU - Österblad, Markus

AU - Helmby, Helena

AU - Hewitson, James P

AU - Maizels, Rick M

AU - Gigliotti Rothfuchs, Antonio

AU - Nylén, Susanne

PY - 2016/1/27

Y1 - 2016/1/27

N2 - 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.

AB - 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.

KW - Animals

KW - Antigens, Bacterial

KW - Antigens, Helminth

KW - Cell Movement

KW - Chronic Disease

KW - Coinfection

KW - Dendritic Cells

KW - Disease Models, Animal

KW - Disease Susceptibility

KW - Gastrointestinal Diseases

KW - Host-Parasite Interactions

KW - Host-Pathogen Interactions

KW - Lymphocyte Activation

KW - Mice

KW - Mice, Knockout

KW - Mycobacterium Infections

KW - Mycobacterium bovis

KW - Nematode Infections

KW - Receptors, Antigen, T-Cell

KW - Receptors, Transforming Growth Factor beta

KW - Signal Transduction

KW - T-Cell Antigen Receptor Specificity

KW - T-Lymphocyte Subsets

U2 - 10.4049/jimmunol.1500970

DO - 10.4049/jimmunol.1500970

M3 - Article

C2 - 26819205

SN - 0022-1767

VL - 196

SP - 2262

EP - 2271

JO - Journal of Immunology

JF - Journal of Immunology

IS - 5

ER -