T Cell-Derived IL-10 Impairs Host Resistance to Mycobacterium tuberculosis Infection
File(s)
Published version
Author(s)
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.
Date Issued
2017-07-10
Date Acceptance
2017-05-08
Citation
JOURNAL OF IMMUNOLOGY, 2017, 199 (2), pp.613-623
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/).
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000405273600028&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
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