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Infection and Immunity, March 2006, p. 1857-1864, Vol. 74, No. 3
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.3.1857-1864.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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, and Chao-Hung Lee*

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202

Received 6 September 2005/ Returned for modification 18 October 2005/ Accepted 9 December 2005

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-{kappa}B and the production of proinflammatory cytokine tumor necrosis factor alpha (TNF-{alpha}) 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-{kappa}B response to P. murina. TNF-{alpha} and MIP-2 production in response to P. murina by mouse 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-{alpha} 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.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 1120 South Drive, Fesler Hall Rm. 419, Indianapolis, IN 46202. Phone: (317) 274-2596. Fax: (317) 278-0643. E-mail: chlee{at}iupui.edu.

Editor: A. Casadevall

Infection and Immunity, March 2006, p. 1857-1864, Vol. 74, No. 3
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.3.1857-1864.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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