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RP105 facilitates macrophage activation by Mycobacterium tuberculosis lipoproteins.

TitleRP105 facilitates macrophage activation by Mycobacterium tuberculosis lipoproteins.
Publication TypeJournal Article
Year of Publication2009
AuthorsBlumenthal A, Kobayashi T, Pierini LM, Banaei N, Ernst JD, Miyake K, Ehrt S
JournalCell Host Microbe
Volume5
Issue1
Pagination35-46
Date Published2009 Jan 22
ISSN1934-6069
KeywordsAnimals, Antigens, CD, Bacterial Proteins, Cells, Cultured, Cytokines, Lipoproteins, Lung, Macrophage Activation, Macrophages, Mice, Mice, Knockout, Mycobacterium tuberculosis
Abstract

RP105, phylogenetically related to Toll-like receptor (TLR)-4, is reported to facilitate B cell activation by the TLR4-agonist lipopolysaccharide (LPS)--but to limit LPS-induced cytokine production by antigen-presenting cells. Here, we show that the role of RP105 extends beyond LPS recognition and that RP105 positively regulates macrophage responses to Mycobacterium tuberculosis (Mtb) lipoproteins. Mtb-infected RP105(-/-) mice exhibited impaired proinflammatory cytokine responses associated with enhanced bacterial burden and increased lung pathology. The Mtb 19 kDa lipoprotein induced release of tumor necrosis factor in a manner dependent on both TLR2 and RP105, and macrophage activation by Mtb lacking mature lipoproteins was not RP105 dependent. Thus, mycobacterial lipoproteins are RP105 agonists. RP105 physically interacted with TLR2, and both RP105 and TLR2 were required for optimal macrophage activation by Mtb. Our data identify RP105 as an accessory molecule for TLR2, forming part of the receptor complex for innate immune recognition of mycobacterial lipoproteins.

DOI10.1016/j.chom.2008.12.002
Alternate JournalCell Host Microbe
PubMed ID19154986
PubMed Central IDPMC2742161
Grant ListK08 AI061105-05 / AI / NIAID NIH HHS / United States
R01 AI046097-10 / AI / NIAID NIH HHS / United States
R01 AI046097 / AI / NIAID NIH HHS / United States
AI16097 / AI / NIAID NIH HHS / United States
R01 HL068525 / HL / NHLBI NIH HHS / United States
L30 AI061958-01 / AI / NIAID NIH HHS / United States
R01 HL068525-05 / HL / NHLBI NIH HHS / United States
HL68525 / HL / NHLBI NIH HHS / United States
L30 AI061958-02 / AI / NIAID NIH HHS / United States

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