Investigation of the peptidoglycan sensing molecule, PGLYRP-2, in murine inflammatory uveitis.
OBJECTIVE
Peptidoglycan (PGN) recognition proteins (PGLYRPs) are innate immune molecules that recognise bacterial cell wall PGN, and participate in several inflammatory diseases such as arthritis. We sought to elucidate the contribution of PGLYRPs in murine uveitis (intraocular inflammatory disease) elicited by PGN, and the extent to which systemically administered PGN alters uveitis compared with arthritis versus locally triggered ocular responses.


METHODS
Mice deficient for PGLYRP-2, PGLYRP-3 or PGLYRP-4 were administered PGN by an intraperitoneal or intraocular injection. Arthritis was assessed by near-infrared imaging and histopathology, while uveitis was measured by intravital videomicroscopy and histopathology.


RESULTS
Systemic PGN exposure predisposed to arthritis through a PGLYRP-2 dependent mechanism. By contrast, systemic PGN exposure did not predispose to uveitis, and PGLYRP-2 deficiency had no impact on the development the uveitis. When PGN was administered locally, a robust uveitis ensued, which occurred independently of PGLYRP-2. Regardless of whether PGN was administered systemically or locally, neither PGLYRP-3 nor PGLYRP-4 deficiency significantly altered ocular inflammation compared with wild-type control animals.


CONCLUSIONS
Our findings highlight the complexity of PGLYRPs and how PGLYRP-2 may use different molecular pathways in the joints versus eyes. Collectively, our results support a non-essential or redundant role for PGLYRPs-2, -3, -4 in uveitis.
VA Medical Center, Portland, Oregon 97239, USA.
Jenna S
JS
Clowers
Jordan J
JJ
Allensworth
Ellen J
EJ
Lee
Holly L
HL
Rosenzweig
D000818:Animals; D001168:Arthritis / Q000175:diagnosis / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D056965:Injections, Intraocular; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009238:N-Acetylmuramoyl-L-alanine Amidase; D010457:Peptidoglycan / Q000494:pharmacology; D011506:Proteins / Q000502:physiology*; D014605:Uveitis / Q000175:diagnosis / Q000276:immunology*
D010457:Peptidoglycan; D011506:Proteins; D009238:N-Acetylmuramoyl-L-alanine Amidase; C416533:Pglyrp2 protein, mouse