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.
Zhang
Chen
C
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 1120 South Drive, Fesler Hall Rm. 419, Indianapolis, IN 46202, USA.
Wang
Shao-Hung
SH
Lasbury
Mark E
ME
Tschang
Dennis
D
Liao
Chung-Ping
CP
Durant
Pamela J
PJ
Lee
Chao-Hung
CH
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