PGLYRP-2 and Nod2 Are Both Required for Peptidoglycan-Induced Arthritis and Local Inflammation

Sukumar Saha, Jin Qi, Shiyong Wang, Minhui Wang, Xinna Li, Yun Gi Kim, Gabriel Núñez, Dipika Gupta, Roman Dziarski

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Peptidoglycan recognition proteins (PGRPs) are structurally conserved from insects to mammals. Insect PGRPs have diverse host-defense functions. Mammalian PGRPs PGLYRP-1, PGLYRP-3, and PGLYRP-4 have bactericidal activity, while PGLYRP-2 has amidase activity. To extend the known functions of mammalian PGRPs, we examined whether they have immunomodulating activities in peptidoglycan-induced arthritis in mice. We demonstrate that PGLYRP-2 and Nod2 are both required for arthritis in this model. The sequence of events in peptidoglycan-induced arthritis is activation of Nod2, local expression of PGLYRP-2, chemokine production, and recruitment of neutrophils into the limbs, which induces acute arthritis. Only PGLYRP-2 among the four mammalian PGRPs displays this proinflammatory function, and PGLYRP-1 is anti-inflammatory. Toll-like receptor 4 (TLR4) and MyD88 are required for maturation of neutrophils before peptidoglycan challenge. Our results demonstrate that PGRPs, Nod2, and TLR4, representing three different types of pattern-recognition molecules, play interdependent in vivo roles in local inflammation.

Original languageEnglish
Pages (from-to)137-150
Number of pages14
JournalCell Host and Microbe
Volume5
Issue number2
DOIs
Publication statusPublished - 2009 Feb 19
Externally publishedYes

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Keywords

  • CELLBIO
  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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