TY - JOUR
T1 - IL-21 receptor signaling is essential for optimal CD4+ T cell function and control of mycobacterium tuberculosis infection in mice
AU - Cheekatla, Satyanarayana Swamy
AU - Tripathi, Deepak
AU - Venkatasubramanian, Sambasivan
AU - Paidipally, Padmaja
AU - Welch, Elwyn
AU - Tvinnereim, Amy R.
AU - Nurieva, Roza
AU - Vankayalapati, Ramakrishna
N1 - Funding Information:
This work was supported by National Institutes of Health Grants AI123310, AI120257, and A1085135 (to R.V.), U.S. Civilian Research and Development Foundation, The Cain Foundation for Infectious Disease Research, and the Department of Pulmonary Immunology, The University of Texas Health Science Center at Tyler.
Publisher Copyright:
Copyright © 2017 by The American Association of Immunologists, Inc.
PY - 2017/10/15
Y1 - 2017/10/15
N2 - In this study, we determined the role of IL-21R signaling in Mycobacterium tuberculosis infection, using IL-21R knockout (KO) mice. A total of 50% of M. tuberculosis H37Rv-infected IL-21R KO mice died in 6 mo compared with no deaths in infected wild type (WT) mice. M. tuberculosis-infected IL-21R KO mice had enhanced bacterial burden and reduced infiltration of Ag-specific T cells in lungs compared with M. tuberculosis-infected WT mice. Ag-specific T cells from the lungs of M. tuberculosis-infected IL-21R KO mice had increased expression of T cell inhibitory receptors, reduced expression of chemokine receptors, proliferated less, and produced less IFN-g, compared with Ag-specific T cells from the lungs of M. tuberculosis-infected WT mice. T cells from M. tuberculosis-infected IL-21R KO mice were unable to induce optimal macrophage responses to M. tuberculosis. This may be due to a decrease in the Ag-specific T cell population.We also found that IL-21R signaling is associated with reduced expression of a transcriptional factor Eomesodermin and enhanced functional capacity of Ag-specific T cells of M. tuberculosis-infected mice. The sum of our findings suggests that IL-21R signaling is essential for the optimal control of M. tuberculosis infection.
AB - In this study, we determined the role of IL-21R signaling in Mycobacterium tuberculosis infection, using IL-21R knockout (KO) mice. A total of 50% of M. tuberculosis H37Rv-infected IL-21R KO mice died in 6 mo compared with no deaths in infected wild type (WT) mice. M. tuberculosis-infected IL-21R KO mice had enhanced bacterial burden and reduced infiltration of Ag-specific T cells in lungs compared with M. tuberculosis-infected WT mice. Ag-specific T cells from the lungs of M. tuberculosis-infected IL-21R KO mice had increased expression of T cell inhibitory receptors, reduced expression of chemokine receptors, proliferated less, and produced less IFN-g, compared with Ag-specific T cells from the lungs of M. tuberculosis-infected WT mice. T cells from M. tuberculosis-infected IL-21R KO mice were unable to induce optimal macrophage responses to M. tuberculosis. This may be due to a decrease in the Ag-specific T cell population.We also found that IL-21R signaling is associated with reduced expression of a transcriptional factor Eomesodermin and enhanced functional capacity of Ag-specific T cells of M. tuberculosis-infected mice. The sum of our findings suggests that IL-21R signaling is essential for the optimal control of M. tuberculosis infection.
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U2 - 10.4049/jimmunol.1601231
DO - 10.4049/jimmunol.1601231
M3 - Article
C2 - 28855309
AN - SCOPUS:85031507008
SN - 0022-1767
VL - 199
SP - 2815
EP - 2822
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -