UMMS Affiliation

Department of Microbiology and Physiological Systems

Publication Date

11-7-2016

Document Type

Article

Disciplines

Pathogenic Microbiology

Abstract

IL-21 is produced predominantly by activated CD4+ T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (gammac) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8+ T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4+ and CD8+ T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3. We correlate these immune alterations with increased susceptibility of IL-21R-/- mice, which have increased lung bacterial burden and earlier mortality compared to WT mice. Finally, to causally link the immune defects with host susceptibility, we use an adoptive transfer model to show that IL-21R-/- T cells transfer less protection than WT T cells. These results prove that IL-21 signaling has an intrinsic role in promoting the protective capacity of T cells. Thus, the net effect of IL-21 signaling is to enhance host resistance to M. tuberculosis. These data position IL-21 as a candidate biomarker of resistance to tuberculosis.

Rights and Permissions

Copyright © 2016, The Author(s). Citation: Sci Rep. 2016 Nov 7;6:36720. doi: 10.1038/srep36720. Link to article on publisher's site

DOI of Published Version

10.1038/srep36720

Related Resources

Link to Article in PubMed

Keywords

infection, interleukins, pathogens

Journal/Book/Conference Title

Scientific reports

PubMed ID

27819295

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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