PGLYRP-2 and Nod2 are both required for peptidoglycan-induced arthritis and local inflammation

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 mammalia...

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Bibliographic Details
Published in:Cell host & microbe 2009-02, Vol.5 (2), p.137-150
Main Authors: Saha, Sukumar, Qi, Jin, Wang, Shiyong, Wang, Minhui, Li, Xinna, Kim, Yun-Gi, Núñez, Gabriel, Gupta, Dipika, Dziarski, Roman
Format: Article
Language:English
Subjects:
Animals
Arthritis - immunology
Arthritis - pathology
Bacterial Infections - immunology
Bacterial Infections - pathology
Chemokines - secretion
Female
Male
Mice
Mice, Inbred BALB C
Mice, Knockout
N-Acetylmuramoyl-L-alanine Amidase
Neutrophils - immunology
Nod2 Signaling Adaptor Protein - immunology
Peptidoglycan - immunology
Proteins - immunology
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Summary: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.
ISSN:1931-3128
1934-6069
DOI:10.1016/j.chom.2008.12.010