RP105 Facilitates Macrophage Activation by Mycobacterium tuberculosis Lipoproteins

Blumenthal, A., Kobayashi, Toshihiko, Pierini, Lynda M., Banaei, Niaz, Ernst, Joel D., Miyake, Kensuke and Ehrt, Sabine (2009) RP105 Facilitates Macrophage Activation by Mycobacterium tuberculosis Lipoproteins. Cell Host and Microbe, 5 1: 35-46. doi:10.1016/j.chom.2008.12.002


Author Blumenthal, A.
Kobayashi, Toshihiko
Pierini, Lynda M.
Banaei, Niaz
Ernst, Joel D.
Miyake, Kensuke
Ehrt, Sabine
Title RP105 Facilitates Macrophage Activation by Mycobacterium tuberculosis Lipoproteins
Formatted title
RP105 Facilitates Macrophage Activation by Mycobacterium tuberculosis Lipoproteins
Journal name Cell Host and Microbe   Check publisher's open access policy
ISSN 1931-3128
1934-6069
Publication date 2009-01
Sub-type Article (original research)
DOI 10.1016/j.chom.2008.12.002
Volume 5
Issue 1
Start page 35
End page 46
Total pages 12
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
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.
Keyword TOLL-LIKE RECEPTORS
NECROSIS-FACTOR-ALPHA
PATHOGEN RECOGNITION
MOLECULAR-CLONING
INTERFERON-GAMMA
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Thu, 10 Mar 2011, 10:01:10 EST