Toll-like receptor 2 mediates alveolar macrophage response to Pneumocystis murina.
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-kappaB 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-kappaB 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.
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 1120 South Drive, Fesler Hall Rm. 419, Indianapolis, IN 46202, USA.
Chen
C
Zhang
Shao-Hung
SH
Wang
Mark E
ME
Lasbury
Dennis
D
Tschang
Chung-Ping
CP
Liao
Pamela J
PJ
Durant
Chao-Hung
CH
Lee
D000818:Animals; D002460:Cell Line; D054426:Chemokine CXCL2; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000378:metabolism; D011010:Pneumocystis / Q000276:immunology / Q000502:physiology*; D011014:Pneumonia / Q000235:genetics / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D054426:Chemokine CXCL2; D016207:Cytokines; D018836:Inflammation Mediators; D015846:Monokines; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha