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The NOD/RIP2 pathway is essential for host defenses against Chlamydophila pneumoniae lung infection.

Authors: Shimada, K  Chen, S  Dempsey, PW  Sorrentino, R  Alsabeh, R  Slepenkin, AV  Peterson, E  Doherty, TM  Underhill, D  Crother, TR  Arditi, M 
Citation: Shimada K, etal., PLoS Pathog. 2009 Apr;5(4):e1000379. Epub 2009 Apr 10.
Pubmed: (View Article at PubMed) PMID:19360122
DOI: Full-text: DOI:10.1371/journal.ppat.1000379

Here we investigated the role of the Nod/Rip2 pathway in host responses to Chlamydophila pneumoniae-induced pneumonia in mice. Rip2(-/-) mice infected with C. pneumoniae exhibited impaired iNOS expression and NO production, and delayed neutrophil recruitment to the lungs. Levels of IL-6 and IFN-gamma levels as well as KC and MIP-2 levels in bronchoalveolar lavage fluid (BALF) were significantly decreased in Rip2(-/-) mice compared to wild-type (WT) mice at day 3. Rip2(-/-) mice showed significant delay in bacterial clearance from the lungs and developed more severe and chronic lung inflammation that continued even on day 35 and led to increased mortality, whereas WT mice cleared the bacterial load, recovered from acute pneumonia, and survived. Both Nod1(-/-) and Nod2(-/-) mice also showed delayed bacterial clearance, suggesting that C. pneumoniae is recognized by both of these intracellular receptors. Bone marrow chimera experiments demonstrated that Rip2 in BM-derived cells rather than non-hematopoietic stromal cells played a key role in host responses in the lungs and clearance of C. pneumoniae. Furthermore, adoptive transfer of WT macrophages intratracheally was able to rescue the bacterial clearance defect in Rip2(-/-) mice. These results demonstrate that in addition to the TLR/MyD88 pathway, the Nod/Rip2 signaling pathway also plays a significant role in intracellular recognition, innate immune host responses, and ultimately has a decisive impact on clearance of C. pneumoniae from the lungs and survival of the infectious challenge.

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RGD Object Information
RGD ID: 5131449
Created: 2011-04-27
Species: All species
Last Modified: 2011-04-27
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.