Involvement of receptor-interacting protein 2 in innate and adaptive immune responses

Arnold I. Chin, Paul W. Dempsey, Kevin Bruhn, Jeff F. Miller, Yang Xu and Genhong Cheng ()
Additional contact information
Arnold I. Chin: Molecular Biology Institute, University of California
Paul W. Dempsey: Immunology, and Molecular Genetics, Jonsson Comprehensive Cancer Center, University of California
Kevin Bruhn: Immunology, and Molecular Genetics, Jonsson Comprehensive Cancer Center, University of California
Jeff F. Miller: Molecular Biology Institute, University of California
Yang Xu: Section of Molecular Biology, University of California
Genhong Cheng: Molecular Biology Institute, University of California

Nature, 2002, vol. 416, issue 6877, 190-194

Abstract: Abstract Host defences to microorganisms rely on a coordinated interplay between the innate and adaptive responses of immunity1. Infection with intracellular bacteria triggers an immediate innate response requiring macrophages, neutrophils and natural killer cells, whereas subsequent activation of an adaptive response through development of T-helper subtype 1 cells (TH1) proceeds during persistent infection1. To understand the physiological role of receptor-interacting protein 2 (Rip2), also known as RICK and CARDIAK, we generated mice with a targeted disruption of the gene coding for Rip2. Here we show that Rip2-deficient mice exhibit a profoundly decreased ability to defend against infection by the intracellular pathogen Listeria monocytogenes. Rip2-deficient macrophages infected with L. monocytogenes or treated with lipopolysaccharide (LPS) have decreased activation of NF-κB, whereas dominant negative Rip2 inhibited NF-κB activation mediated by Toll-like receptor 4 and Nod1. In vivo, Rip2-deficient mice were resistant to the lethal effects of LPS-induced endotoxic shock. Furthermore, Rip2 deficiency results in impaired interferon-γ production in both TH1 and natural killer cells, attributed in part to defective interleukin-12-induced Stat4 activation. Our data reflect requirements for Rip2 in multiple pathways regulating immune and inflammatory responses.

Date: 2002
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/416190a Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:416:y:2002:i:6877:d:10.1038_416190a

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/416190a

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().