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X. Huang, W. Du, P. Zhang, K. Zhang, M. Sun, L. D. Hazlett, R. P. Barrett; TREM -1 Amplifies Corneal Inflammation After P. aeruginosa Infection by Modulating Th1-/Th2-Type Immune Response. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3902.
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© ARVO (1962-2015); The Authors (2016-present)
To elucidate the role of TREM-1 (Triggering receptors expressed on myeloid cells 1) in Pseudomonas aeruginosa (P. aeruginosa) keratitis.
TREM-1 expression in C57BL/6 (B6) vs BALB/c corneas before and after P. aeruginosa (5 µl of 106 CFU/µl, ATCC stain 19660) challenge was tested by real-time PCR and immunostaining. A soluble mTREM-1/Fc fusion protein or IgG/Fc (control) was used to block TREM-1 signaling in B6 mice by subconjunctival injection. The corneal disease response was monitored in the two groups by slit lamp, clinical score, histopathology, plate counts, real-time PCR and ELISA. After cross-linking activation of TREM-1 with anti-TREM-1 Ab or IgG (control) and LPS stimulation in vitro, production of pro-inflammatory cytokines in macrophages was tested by real-time PCR and ELISA.
TREM-1 was constitutively expressed and disparately up-regulated in the cornea of B6 vs BALB/c mice at 3 and 5 days p.i. Immunostaining further confirmed the TREM-1 expression in infected B6 corneas at 1 and 5 days p.i. To determine whether TREM-1 dictated the susceptible outcome to P. aeruginosa keratitis, a soluble mTREM-1/Fc fusion protein was used as a decoy to blocking TREM-1 signaling in B6 mice. Decreased corneal opacity, stromal damage and bacterial load were displayed after treatment with mTREM-1/Fc fusion protein. Moreover, RT-PCR data demonstrated that blockage of TREM-1 up-regulated Th2-type cytokines such as IL-4, IL-5 and IL-10, while down-regulating Th1-type cytokines including IFN-γ, IL-1β and IL-6. In addition, in vitro studies indicated that cross-linking activation of TREM-1 and LPS stimulation also elevated production of pro-inflammatory cytokines including IL-1β, MIP-2, TNF-α and IL-6.
TREM-1 is disparately up-regulated in B6 vs BALB/c corneas after P. aeruginosa infection, and contributes to the susceptible outcome to P. aeruginosa keratitis by amplifying Th1- vs Th2-type immune responses.
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