Affiliation:
1. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202
Abstract
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 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-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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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