Abstract
Purpose: :
To elucidate the role of triggering receptors expressed on myeloid cells 2 (TREM-2) in Pseudomonas aeruginosa (P. aeruginosa) corneal infection.
Methods: :
mRNA levels of TREM-2 in normal and infected corneas of BALB/c vs C57BL/6 (B6) mice were tested by real-time RT-PCR. The distribution patterns of TREM-2 in BALB/c mice were further determined by immunostaining before and at 5 days postinfection (p.i.). For in vivo study, BALB/c mice were treated with TREM-2 siRNA by subconjunctival injection and then topical application. Disease was monitored using slit lamp, bacterial plate counts and MPO assay. Pro-inflammatory cytokines/chemokines for both in vivo and in vitro were tested by RT-PCR and ELISA.
Results: :
TREM-2 is constitutively expressed and disparately up-regulated in BALB/c vs B6 corneas after P. aeruginosa infection. Increased corneal opacity and worsened disease were displayed after silencing TREM-2. TREM-2 silencing also increased bacterial load and neutrophil (PMN) infiltration in BALB/c corneas. RT-PCR and ELISA data further demonstrated that silencing TREM-2 significantly enhanced the expression of Th1-type and pro-inflammatory cytokines (e.g., IFN-γ, IL-18, MIP-2, TNF-α, IL-1β, IL-6), but reduced the expression of Th2-type cytokines (e.g., IL-4, IL-5, IL-10). In addition, in vitro studies demonstrated that TREM-2 inhibits pro-inflammatory cytokine production through a PI3K signal pathway.
Conclusions: :
TREM-2 is disparately up-regulated in BALB/c vs B6 corneas after P. aeruginosa infection, and contributes to the host resistance by amplifying Th2- vs Th1-type immune responses through PI3K signaling.
Keywords: inflammation • immunomodulation/immunoregulation • cornea: basic science