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
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 (...
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doaj-7fc6cfa80e9443f985c5e473de8e5ae62020-11-25T01:46:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-10-01910.3389/fimmu.2018.02317390568Presence 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 MiceKetema Abdissa0Ketema Abdissa1Andreas Nerlich2Andreas Beineke3Nanthapon Ruangkiattikul4Vinay Pawar5Ulrike Heise6Nina Janze7Christine Falk8Dunja Bruder9Dunja Bruder10Ulrike Schleicher11Ulrike Schleicher12Christian Bogdan13Christian Bogdan14Siegfried Weiss15Siegfried Weiss16Ralph Goethe17Institute for Microbiology, University of Veterinary Medicine Hannover, Hannover, GermanyDepartment of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyInstitute for Microbiology, University of Veterinary Medicine Hannover, Hannover, GermanyInstitute for Pathology, University of Veterinary Medicine Hannover, Hannover, GermanyInstitute for Microbiology, University of Veterinary Medicine Hannover, Hannover, GermanyDepartment of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyMouse Pathology, Helmholtz Centre for Infection Research, Braunschweig, GermanyInstitute for Microbiology, University of Veterinary Medicine Hannover, Hannover, GermanyInstitute of Transplant Immunology, Hannover Medical School, Hannover, GermanyImmune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, GermanyInstitute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University Magdeburg, Magdeburg, GermanyMikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, GermanyMedical Immunology Campus Erlangen, FAU Erlangen-Nürnberg, Erlangen, GermanyMikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, GermanyMedical Immunology Campus Erlangen, FAU Erlangen-Nürnberg, Erlangen, GermanyDepartment of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany0Institute of Immunology, Hannover Medical School, Hannover, GermanyInstitute for Microbiology, University of Veterinary Medicine Hannover, Hannover, GermanyMyeloid-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.https://www.frontiersin.org/article/10.3389/fimmu.2018.02317/fullMDSCnon-tuberculous mycobacteriaT cellsdendritic cellsiNOSNos2 |
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language |
English |
format |
Article |
sources |
DOAJ |
author |
Ketema Abdissa Ketema Abdissa Andreas Nerlich Andreas Beineke Nanthapon Ruangkiattikul Vinay Pawar Ulrike Heise Nina Janze Christine Falk Dunja Bruder Dunja Bruder Ulrike Schleicher Ulrike Schleicher Christian Bogdan Christian Bogdan Siegfried Weiss Siegfried Weiss Ralph Goethe |
spellingShingle |
Ketema Abdissa Ketema Abdissa Andreas Nerlich Andreas Beineke Nanthapon Ruangkiattikul Vinay Pawar Ulrike Heise Nina Janze Christine Falk Dunja Bruder Dunja Bruder Ulrike Schleicher Ulrike Schleicher Christian Bogdan Christian Bogdan Siegfried Weiss Siegfried Weiss Ralph Goethe 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 MDSC non-tuberculous mycobacteria T cells dendritic cells iNOS Nos2 |
author_facet |
Ketema Abdissa Ketema Abdissa Andreas Nerlich Andreas Beineke Nanthapon Ruangkiattikul Vinay Pawar Ulrike Heise Nina Janze Christine Falk Dunja Bruder Dunja Bruder Ulrike Schleicher Ulrike Schleicher Christian Bogdan Christian Bogdan Siegfried Weiss Siegfried Weiss Ralph Goethe |
author_sort |
Ketema Abdissa |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-10-01 |
description |
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. |
topic |
MDSC non-tuberculous mycobacteria T cells dendritic cells iNOS Nos2 |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.02317/full |
work_keys_str_mv |
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