Purchase this article with an account.
Y. Sun, R. Ramadan, M. Karmakar, S. Roy, A. Rietsch, E. Pearlman; Innate Immunity in Pseudomonas aeruginosa Keratitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3442.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Corneas of C57BL/6 and gene knockout mice three parallel abrasions, and were infected with 1 x 103 PA strain 19660 or PAO1, or with flagellin (ΔfliC) mutants derived from these strains. Flow cytometry, cytokine production, neutrophil myeloperoxidase (MPO) and bacterial colony forming units (CFU) were measured by standard methods.
1) CD11b+ macrophages in the cornea selectively expressed surface TLR4 and TLR5; 2) macrophage depleted (Mafia) mice had significantly elevated CFU, but lower cytokine production and cellular infiltration to the cornea compared with control mice; 3) TLR4-/- and MD-2-/- mice had significantly increased CFU, decreased cytokine production and MPO compared with C57BL/6 after infection with ΔfliC mutants, and which required TLR4 expression on bone marrow cells. There was no significant difference in CFU after infection with PA strains expressing flagella; 4) TLR4/5 -/- but not TLR5 -/- mice had elevated CFU after infection with PA strains expressing flagella; 5) PA incubated with bone marrow macrophages induced TRIF -dependent IRF3 phosphorylation in addition to TIRAP/MyD88 dependent IΚB phosphorylation and p65 nuclear translocation; 6) MyD88-/- and TRIF-/- mice had elevated CFU and decreased MPO levels compared with TIRAP-/- and C57BL/6 mice; and 7) IL-1R1-/- and IL-1α/β-/- mice, but not IL-1α-/- or IL-1β-/- mice had elevated CFU and decreased cellular infiltration compared with C57BL/6 mice.
These findings indicate that PA is recognized by TLR4/MD-2 and TLR5 expressed on corneal macrophages, which activate both the MyD88/TIRAP and TRIF pathways to produce CXCL1/KC, IL-1α and IL-1β. IL-1R1/MyD88 signaling also produces CXCL1/KC, resulting in neutrophil recruitment to the corneal stroma and subsequent bacterial killing.
This PDF is available to Subscribers Only