Phosphorylated STAT3 and PD-1 regulate IL-17 production and IL-23 receptor expression in Mycobacterium tuberculosis infection

被引:49
作者
Bandaru, Anuradha [1 ]
Devalraju, Kamakshi P. [1 ]
Paidipally, Padmaja [2 ,3 ]
Dhiman, Rohan [2 ,3 ]
Venkatasubramanian, Sambasivan [2 ,3 ]
Barnes, Peter F. [2 ,3 ,4 ]
Vankayalapati, Ramakrishna [2 ,3 ]
Valluri, Vijayalakshmi [1 ]
机构
[1] LEPRA Soc, Blue Peter Res Ctr, Hyderabad 501301, Andhra Pradesh, India
[2] Univ Texas Hlth Ctr Tyler, CPIDC, Tyler, TX 75708 USA
[3] Univ Texas Hlth Ctr Tyler, Ctr Biomed Res, Dept Microbiol & Immunol, Tyler, TX 75708 USA
[4] Univ Texas Hlth Ctr Tyler, Ctr Biomed Res, Dept Med, Tyler, TX 75708 USA
基金
美国国家卫生研究院;
关键词
Cytokine; Human; IL-17; M; tuberculosis; T-CELL RESPONSES; ACTIVE TUBERCULOSIS; TH17; CELLS; HOST-DEFENSE; DEATH; GAMMA; DIFFERENTIATION; INTERLEUKIN-17; IMMUNITY; INNATE;
D O I
10.1002/eji.201343680
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We studied the factors that regulate IL-23 receptor expression and IL-17 production in human tuberculosis infection. Mycobacterium tuberculosis (M. tb)-stimulated CD4(+) T cells from tuberculosis patients secreted less IL-17 than did CD4(+) T cells from healthy tuberculin reactors (PPD+). M. tb-cultured monocytes from tuberculosis patients and PPD+ donors expressed equal amounts of IL-23p19 mRNA and protein, suggesting that reduced IL-23 production is not responsible for decreased IL-17 production by tuberculosis patients. Freshly isolated and M. tb-stimulated CD4(+) T cells from tuberculosis patients had reduced IL-23 receptor and phosphorylated STAT3 (pSTAT3) expression, compared with cells from PPD+ donors. STAT3 siRNA reduced IL-23 receptor expression and IL-17 production by CD4(+) T cells from PPD+ donors. Tuberculosis patients had increased numbers of PD-1(+) T cells compared with healthy PPD+ individuals. Anti-PD-1 antibody enhanced pSTAT3 and IL-23R expression and IL-17 production by M. tb-cultured CD4(+) T cells of tuberculosis patients. Anti-tuberculosis therapy decreased PD-1 expression, increased IL-17 and IFN-gamma production and pSTAT3 and IL-23R expression. These findings demonstrate that increased PD-1 expression and decreased pSTAT3 expression reduce IL-23 receptor expression and IL-17 production by CD4(+) T cells of tuberculosis patients.
引用
收藏
页码:2013 / 2024
页数:12
相关论文
共 58 条
  • [1] Antonysamy MA, 1999, J IMMUNOL, V162, P577
  • [2] CD4 T Cells Promote Rather than Control Tuberculosis in the Absence of PD-1-Mediated Inhibition
    Barber, Daniel L.
    Mayer-Barber, Katrin D.
    Feng, Carl G.
    Sharpe, Arlene H.
    Sher, Alan
    [J]. JOURNAL OF IMMUNOLOGY, 2011, 186 (03) : 1598 - 1607
  • [3] Reduced Th17 Response in Patients with Tuberculosis Correlates with IL-6R Expression on CD4+ T Cells
    Chen, Xinchun
    Zhang, Mingxia
    Liao, Mingfeng
    Graner, Michael W.
    Wu, Changyou
    Yang, Qianting
    Liu, Haiying
    Zhou, Boping
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2010, 181 (07) : 734 - 742
  • [4] Candida albicans Dampens Host Defense by Downregulating IL-17 Production
    Cheng, Shih-Chin
    van de Veerdonk, Frank
    Smeekens, Sanne
    Joosten, Leo A. B.
    van der Meer, Jos W. M.
    Kullberg, Bart-Jan
    Netea, Mihai G.
    [J]. JOURNAL OF IMMUNOLOGY, 2010, 185 (04) : 2450 - 2457
  • [5] Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis
    Conti, Heather R.
    Shen, Fang
    Nayyar, Namrata
    Stocum, Eileen
    Sun, Jianing N.
    Lindemann, Matthew J.
    Ho, Allen W.
    Hai, Justine Hoda
    Yu, Jeffrey J.
    Jung, Ji Won
    Filler, Scott G.
    Masso-Welch, Patricia
    Edgerton, Mira
    Gaffen, Sarah L.
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (02) : 299 - 311
  • [6] Comparison of interferon-γ-, interleukin (IL)-17- and IL-22-expressing CD4 T cells, IL-22-expressing granulocytes and proinflammatory cytokines during latent and active tuberculosis infection
    Cowan, J.
    Pandey, S.
    Filion, L. G.
    Angel, J. B.
    Kumar, A.
    Cameron, D. W.
    [J]. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2012, 167 (02) : 317 - 329
  • [7] CD5 costimulation induces stable Th17 development by promoting IL-23R expression and sustained STAT3 activation
    de Wit, Jelle
    Souwer, Yuri
    van Beelen, Astrid J.
    de Groot, Rosa
    Muller, Femke J. M.
    Bos, Hanny Klaasse
    Jorritsma, Tineke
    Kapsenberg, Martien L.
    de Jong, Esther C.
    van Ham, Marieke
    [J]. BLOOD, 2011, 118 (23) : 6107 - 6114
  • [8] Immunology of tuberculosis
    Flynn, JL
    Chan, J
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2001, 19 : 93 - 129
  • [9] MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I-RESTRICTED T-CELLS ARE REQUIRED FOR RESISTANCE TO MYCOBACTERIUM-TUBERCULOSIS INFECTION
    FLYNN, JL
    GOLDSTEIN, MM
    TRIEBOLD, KJ
    KOLLER, B
    BLOOM, BR
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (24) : 12013 - 12017
  • [10] Mannose-capped lipoarabinomannan- and prostaglandin E2-dependent expansion of regulatory T cells in human Mycobacterium tuberculosis infection
    Garg, Ankita
    Barnes, Peter F.
    Roy, Sugata
    Quiroga, Maria F.
    Wu, Shiping
    Garcia, Veronica E.
    Krutzik, Stephan R.
    Weis, Steven E.
    Vankayalapati, Ramakrishna
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2008, 38 (02) : 459 - 469