TREM-2 Promotes Host Resistance Against Pseudomonas aeruginosa Infection by Suppressing Corneal Inflammation via a PI3K/Akt Signaling Pathway
Year: 2013
Type: article
Abstract: PURPOSE: To explore the role of triggering receptor expressed on myeloid cells 2 (TREM-2) in Pseudomonas aeruginosa (PA) keratitis. METHODS: BALB/c mice were routinely infected with PA and evaluated at various postinfection time points for corneal expression of TREM-2, by real-time PCR, Western blot, and flow cytometry. Next, BALB/c and C57BL/6 mice were respectively treated with TREM-2 siRNA or agonistic anti-TREM-2 antibody, to determine the role of TREM-2 in PA keratitis. Bacterial load and neutrophil infiltration were tested by plate count and myeloperoxidase assay, respectively. Th1-/Th2-type and proinflammatory cytokine expression were tested by real-time PCR and ELISA after in vivo and in vitro silencing of TREM-2. Moreover, phosphorylated Akt levels were tested by Western blot in murine macrophages after treatment with agonistic anti-TREM-2 antibody. mRNA levels of proinflammatory cytokines were examined in murine macrophages after TREM-2 activation and lipopolysaccharide stimulation, following pretreatment with inhibitors for PI3K or Akt, to determine whether PI3K/Akt is required in TREM-2-mediated immune modulation. In addition, BALB/c mice were treated with wortmannin and analyzed for bacterial load and proinflammatory cytokine expression. RESULTS: TREM-2 expression was elevated in the infected BALB/c corneas at 3 or 5 days postinfection. Silencing of TREM-2 accelerated disease progression by enhancing bacterial load and corneal inflammation, whereas activation of TREM-2 promoted host resistance to PA keratitis. PI3K/Akt signaling is required in the TREM-2-mediated immune modulation, and inhibition of PI3K resulted in worsened disease after PA corneal infection. CONCLUSIONS: TREM-2 promoted host resistance to PA infection by suppressing corneal inflammation via activation of the PI3K/Akt pathway.
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, State Key Laboratory of Ophthalmology, National Institutes of Health, Guangdong Province Introduction of Innovative R&D Team, Specialized Research Fund for the Doctoral Program of Higher Education of China, National Eye Institute
Awards: G1022687494, G1479137238, G156324800, Attacking the Global Problem of Antimicrobial Resistance, G2037558836, G2072431842, G2104499215, G421110680, G4224273064, G4708718232, G5381977887, G5401515598, G5751125607, G6589828840, Role of Triggering Receptors Expressed on Myeloid Cells in Bacterial Keratitis, G841709106, Core Grant for Vision Research
OpenAlex ID: W2089938014