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T Cell-Derived IL-10 Impairs Host Resistance to Mycobacterium tuberculosis Infection

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Moreira_Teixiera IL-10 T cells Mtb JImmunol 2017.pdfPublished version2.15 MBAdobe PDFView/Open
Title: T Cell-Derived IL-10 Impairs Host Resistance to Mycobacterium tuberculosis Infection
Authors: Moreira-Teixeira, L
Redford, PS
Stavropoulos, E
Ghilardi, N
Maynard, CL
Weaver, CT
Freitas do Rosario, AP
Wu, X
Langhorne, J
O'Garra, A
Item Type: Journal Article
Abstract: Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, is a leading cause of mortality and morbidity, causing ∼1.5 million deaths annually. CD4+ T cells and several cytokines, such as the Th1 cytokine IFN-γ, are critical in the control of this infection. Conversely, the immunosuppressive cytokine IL-10 has been shown to dampen Th1 cell responses to M. tuberculosis infection impairing bacterial clearance. However, the critical cellular source of IL-10 during M. tuberculosis infection is still unknown. Using IL-10 reporter mice, we show in this article that during the first 14 d of M. tuberculosis infection, the predominant cells expressing IL-10 in the lung were Ly6C+ monocytes. However, after day 21 postinfection, IL-10–expressing T cells were also highly represented. Notably, mice deficient in T cell–derived IL-10, but not mice deficient in monocyte-derived IL-10, showed a significant reduction in lung bacterial loads during chronic M. tuberculosis infection compared with fully IL-10–competent mice, indicating a major role for T cell–derived IL-10 in TB susceptibility. IL-10–expressing cells were detected among both CD4+ and CD8+ T cells, expressed high levels of CD44 and Tbet, and were able to coproduce IFN-γ and IL-10 upon ex vivo stimulation. Furthermore, during M. tuberculosis infection, Il10 expression in CD4+ T cells was partially regulated by both IL-27 and type I IFN signaling. Together, our data reveal that, despite the multiple immune sources of IL-10 during M. tuberculosis infection, activated effector T cells are the major source accounting for IL-10–induced TB susceptibility.
Issue Date: 10-Jul-2017
Date of Acceptance: 8-May-2017
URI: http://hdl.handle.net/10044/1/51720
DOI: https://dx.doi.org/10.4049/jimmunol.1601340
ISSN: 0022-1767
Publisher: American Association of Immunologists, Inc.
Start Page: 613
End Page: 623
Journal / Book Title: JOURNAL OF IMMUNOLOGY
Volume: 199
Issue: 2
Copyright Statement: © 2017 The Authors. This article is distributed under the terms of the CC BY 4.0 Unported license (https://creativecommons.org/licenses/by/4.0/).
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
IMMUNE-RESPONSES
INTERFERON-GAMMA
PULMONARY TUBERCULOSIS
ACTIVE TUBERCULOSIS
PROTECTIVE IMMUNITY
CYTOKINE PRODUCTION
VIRUS-INFECTION
TH1 RESPONSES
IFN-GAMMA
TGF-BETA
1107 Immunology
Publication Status: Published
Appears in Collections:National Heart and Lung Institute