Toll-like receptor 2 mediates alveolar macrophage response to Pneumocystis murina

Chen Zhang, Shao Hung Wang, Mark E. Lasbury, Dennis Tschang, Chung Ping Liao, Pamela J. Durant, Chao Hung Lee

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

The innate immune response to Pneumocystis infection is not well understood. In this study, normal C57BL/6 mouse alveolar macrophages were found to respond to Pneumocystis murina organisms through Toll-like receptor 2 (TLR2), leading to the nuclear translocation of NF-κB and the production of proinflammatory cytokine tumor necrosis factor alpha (TNF-α) and chemokine macrophage inflammatory protein 2 (MIP-2). P. murina stimulation of normal alveolar macrophages from C57BL/6 mice resulted in increased TLR2 transcription but not increased TLR4 transcription. In gain-of-function studies with HEK293 cells expressing TLR2 or TLR4, only TLR2 was found to stimulate an NF-κB response to P. murina. TNF-α and MIP-2 production in response to P. murina by moose alveolar macrophages was inhibited by a monoclonal antibody that specifically blocked the ligand-binding ability of TLR2. Alveolar macrophages from TLR2 knockout (TLR2-/-) mice showed little increase in TNF-α and MIP-2 mRNA levels upon P. murina stimulation. An in vivo study showed that TLR2-/- mice challenged with P. murina had reduced cytokine responses. These results indicate that TLR2 plays a major role in the innate immune response to P. murina.

Original languageEnglish (US)
Pages (from-to)1857-1864
Number of pages8
JournalInfection and immunity
Volume74
Issue number3
DOIs
StatePublished - Mar 1 2006

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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  • Cite this

    Zhang, C., Wang, S. H., Lasbury, M. E., Tschang, D., Liao, C. P., Durant, P. J., & Lee, C. H. (2006). Toll-like receptor 2 mediates alveolar macrophage response to Pneumocystis murina. Infection and immunity, 74(3), 1857-1864. https://doi.org/10.1128/IAI.74.3.1857-1864.2006