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

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-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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Zhang C,Wang SH,Lasbury ME,Tschang D,Liao CP,Durant PJ,Lee CH

doi

10.1128/IAI.74.3.1857-1864.2006

keywords:

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

1857-64

issue

3

eissn

0019-9567

issn

1098-5522

pii

74/3/1857

journal_volume

74

pub_type

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