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 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.
Saha
Sukumar
S
Indiana University School of Medicine Northwest, Gary, IN 46408, USA.
Qi
Jin
J
Wang
Shiyong
S
Wang
Minhui
M
Li
Xinna
X
Kim
Yun-Gi
YG
Núñez
Gabriel
G
Gupta
Dipika
D
Dziarski
Roman
R
D000818:Animals; D001168:Arthritis / Q000276:immunology* / Q000473:pathology; D001424:Bacterial Infections / Q000276:immunology* / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009238:N-Acetylmuramoyl-L-alanine Amidase; D009504:Neutrophils / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology*; D010457:Peptidoglycan / Q000276:immunology*; D011506:Proteins / Q000276:immunology*
D018925:Chemokines; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D010457:Peptidoglycan; D011506:Proteins; D009238:N-Acetylmuramoyl-L-alanine Amidase; C416533:Pglyrp2 protein, mouse