Mycobacterium tuberculosis lipoproteins directly regulate human memory CD4+ T cell activation via toll-like receptors 1 and 2

Christina Lancioni, Qing Li, Jeremy J. Thomas, XueDong Ding, Bonnie Thiel, Michael G. Drage, Nicole D. Pecora, Assem G. Ziady, Samuel Shank, Clifford V. Harding, W. Henry Boom, Roxana E. Rojas

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The success of Mycobacterium tuberculosis as a pathogen relies on its ability to regulate the host immune response. M. tuberculosis can manipulate adaptive T cell responses indirectly by modulating antigen-presenting cell (APC) function or by directly interacting with T cells. Little is known about the role of M. tuberculosis molecules in direct regulation of T cell function. Using a biochemical approach, we identified lipoproteins LprG and LpqH as major molecules in M. tuberculosis lysate responsible for costimulation of primary human CD4+ T cells. In the absence of APCs, activation of memory CD4+ T cells with LprG or LpqH in combination with anti-CD3 antibody induces Th1 cytokine secretion and cellular proliferation. Lipoprotein-induced T cell costimulation was inhibited by blocking antibodies to Toll-like receptor 2 (TLR2) and TLR1, indicating that human CD4+ T cells can use TLR2/TLR1 heterodimers to directly respond to M. tuberculosis products. M. tuberculosis lipoproteins induced NF-κB activation in CD4+ T cells in the absence of TCR co-engagement. Thus, TLR2/TLR1 engagement alone by M. tuberculosis lipoprotein triggered intracellular signaling, but upregulation of cytokine production and proliferation required co-engagement of the TCR. In conclusion, our results demonstrate that M. tuberculosis lipoproteins LprG and LpqH participate in the regulation of adaptive immunity not only by inducing cytokine secretion and costimulatory molecules in innate immune cells but also through directly regulating the activation of memory T lymphocytes.

Original languageEnglish (US)
Pages (from-to)663-673
Number of pages11
JournalInfection and Immunity
Volume79
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

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Toll-Like Receptor 1
Toll-Like Receptor 2
Mycobacterium tuberculosis
Lipoproteins
T-Lymphocytes
Cytokines
Blocking Antibodies
Adaptive Immunity
Antigen-Presenting Cells
Anti-Idiotypic Antibodies
Up-Regulation
Cell Proliferation

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Mycobacterium tuberculosis lipoproteins directly regulate human memory CD4+ T cell activation via toll-like receptors 1 and 2. / Lancioni, Christina; Li, Qing; Thomas, Jeremy J.; Ding, XueDong; Thiel, Bonnie; Drage, Michael G.; Pecora, Nicole D.; Ziady, Assem G.; Shank, Samuel; Harding, Clifford V.; Boom, W. Henry; Rojas, Roxana E.

In: Infection and Immunity, Vol. 79, No. 2, 02.2011, p. 663-673.

Research output: Contribution to journalArticle

Lancioni, C, Li, Q, Thomas, JJ, Ding, X, Thiel, B, Drage, MG, Pecora, ND, Ziady, AG, Shank, S, Harding, CV, Boom, WH & Rojas, RE 2011, 'Mycobacterium tuberculosis lipoproteins directly regulate human memory CD4+ T cell activation via toll-like receptors 1 and 2', Infection and Immunity, vol. 79, no. 2, pp. 663-673. https://doi.org/10.1128/IAI.00806-10
Lancioni, Christina ; Li, Qing ; Thomas, Jeremy J. ; Ding, XueDong ; Thiel, Bonnie ; Drage, Michael G. ; Pecora, Nicole D. ; Ziady, Assem G. ; Shank, Samuel ; Harding, Clifford V. ; Boom, W. Henry ; Rojas, Roxana E. / Mycobacterium tuberculosis lipoproteins directly regulate human memory CD4+ T cell activation via toll-like receptors 1 and 2. In: Infection and Immunity. 2011 ; Vol. 79, No. 2. pp. 663-673.
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