Format

Send to

Choose Destination
See comment in PubMed Commons below
FEMS Immunol Med Microbiol. 2012 Nov;66(2):211-9. doi: 10.1111/j.1574-695X.2012.01001.x. Epub 2012 Jul 23.

Receptor interacting protein-2 contributes to host defense against Anaplasma phagocytophilum infection.

Author information

1
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. bindu.sukumaran@duke-nus.edu.sg

Abstract

The Gram-negative obligate intracellular bacterium Anaplasma phagocytophilum is the causative agent of human granulocytic anaplasmosis (HGA), an emerging tick-borne infectious disease occurring worldwide. HGA is generally self-limiting; however, the underlying mechanisms, particularly the innate immune pathways that mediate the immune clearance of A. phagocytophilum, are less understood. We herein report an unexpected role for Receptor interacting protein-2 (Rip2), the adaptor protein for the Nod-like receptors (NLRs), Nod1/Nod2, in the host immune response against A. phagocytophilum infection. Although A. phagocytophilum genome is reported to lack the genes encoding the known ligands of Nod1 and Nod2, its infection upregulated the transcription of Rip2 in human primary neutrophils. Our results revealed that Rip2-deficient mice had significantly higher bacterial load than wild-type controls throughout the infection period. In addition, the Rip2-deficient mice took strikingly longer duration to clear A. phagocytophilum infection. Detailed analysis identified that interferon gamma (IFNγ) and interleukin (IL)-18 but not IL-12, macrophage inflammatory protein-2, and KC response were diminished in A. phagocytophilum-challenged Rip2-deficient mice. Together, these results revealed that Rip2 plays important roles in the immune control of A. phagocytophilum and may contribute to our understanding of the host response to Rickettsiales.

PMID:
22747758
PMCID:
PMC3530031
DOI:
10.1111/j.1574-695X.2012.01001.x
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Support Center