Presence of Infected Gr-1intCD11bhiCD11cint Monocytic Myeloid Derived Suppressor Cells Subverts T Cell Response and Is Associated With Impaired Dendritic Cell Function in Mycobacterium avium-Infected Mice

Abdissa K, Nerlich A, Beineke A, Ruangkiattikul N, Pawar V, Heise U, Janze N, Falk C, Bruder D, Schleicher U, Bogdan C, Weiss S, Goethe R (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 9

DOI: 10.3389/fimmu.2018.02317

Abstract

Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with immunomodulatory function. To study the mechanism by which MDSC affect antimicrobial immunity, we infected mice with two M. avium strains of differential virulence, highly virulent Mycobacterium avium subsp. avium strain 25291 (MAA) and low virulent Mycobacterium avium subsp. hominissuis strain 104 (MAH). Intraperitoneal infection with MAA, but not MAH, caused severe disease and massive splenic infiltration of monocytic MDSC (M-MDSC; Gr-1intCD11bhiCD11cint) expressing inducible NO synthase (Nos2) and bearing high numbers of mycobacteria. Depletion experiments demonstrated that M-MDSC were essential for disease progression. NO production by M-MDSC influenced antigen-uptake and processing by dendritic cells and proliferation of CD4+ T cells. M-MDSC were also induced in MAA-infected mice lacking Nos2. In these mice CD4+ T cell expansion and control of infection were restored. However, T cell inhibition was only partially relieved and arginase (Arg) 1-expressing M-MDSC were accumulated. Likewise, inhibition of Arg1 also partially rescued T cell proliferation. Thus, mycobacterial virulence results in the induction of M-MDSC that block the T cell response in a Nos2- and Arg1-dependent manner.

Authors with CRIS profile

Ulrike Schleicher Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Christian Bogdan Lehrstuhl für Mikrobiologie und Infektionsimmunologie

Involved external institutions

Stiftung Tierärztliche Hochschule Hannover (TiHo) DE Germany (DE) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE)

How to cite

APA:

Abdissa, K., Nerlich, A., Beineke, A., Ruangkiattikul, N., Pawar, V., Heise, U.,... Goethe, R. (2018). Presence of Infected Gr-1intCD11bhiCD11cint Monocytic Myeloid Derived Suppressor Cells Subverts T Cell Response and Is Associated With Impaired Dendritic Cell Function in Mycobacterium avium-Infected Mice. Frontiers in Immunology, 9. https://doi.org/10.3389/fimmu.2018.02317

MLA:

Abdissa, Ketema, et al. "Presence of Infected Gr-1intCD11bhiCD11cint Monocytic Myeloid Derived Suppressor Cells Subverts T Cell Response and Is Associated With Impaired Dendritic Cell Function in Mycobacterium avium-Infected Mice." Frontiers in Immunology 9 (2018).

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