The Cytosolic Sensors Nod1 and Nod2 Are Critical for Bacterial Recognition and Host Defense after Exposure to Toll-like Receptor Ligands

Yun Gi Kim, Jong Hwan Park, Michael H. Shaw, Luigi Franchi, Naohiro Inohara, Gabriel Núñez

研究成果: Article

203 引用 (Scopus)

抜粋

The cytosolic sensors Nod1 and Nod2 and Toll-like receptors (TLRs) activate defense signaling pathways in response to microbial stimuli. However, the role of Nod1 and Nod2 and their interplay with TLRs during systemic bacterial infection remains poorly understood. Here, we report that macrophages or mice made insensitive to TLRs by previous exposure to microbial ligands remained responsive to Nod1 and Nod2 stimulation. Furthermore, Nod1- and Nod2-mediated signaling and gene expression are enhanced in TLR-tolerant macrophages. Further analyses revealed that innate immune responses induced by bacterial infection relied on Nod1 and Nod2 and their adaptor RICK in macrophages pretreated with TLR ligands but not in naive macrophages. In addition, bacterial clearance upon systemic infection with L. monocytogenes was critically dependent on Nod1 and Nod2 when mice were previously stimulated with lipopolysaccharide or E. coli. Thus, Nod1 and Nod2 are important for microbial recognition and host defense after TLR stimulation.

元の言語English
ページ(範囲)246-257
ページ数12
ジャーナルImmunity
28
発行部数2
DOI
出版物ステータスPublished - 2008 2 15
外部発表Yes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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