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TREM-2 promotes host resistance against Pseudomonas aeruginosa infection by suppressing corneal inflammation via a PI3K/Akt signaling pathway.
Invest Ophthalmol Vis Sci 2013; 54(5):3451-62IO

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.

Authors+Show Affiliations

Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23611998

Citation

Sun, Mingxia, et al. "TREM-2 Promotes Host Resistance Against Pseudomonas Aeruginosa Infection By Suppressing Corneal Inflammation Via a PI3K/Akt Signaling Pathway." Investigative Ophthalmology & Visual Science, vol. 54, no. 5, 2013, pp. 3451-62.
Sun M, Zhu M, Chen K, et al. TREM-2 promotes host resistance against Pseudomonas aeruginosa infection by suppressing corneal inflammation via a PI3K/Akt signaling pathway. Invest Ophthalmol Vis Sci. 2013;54(5):3451-62.
Sun, M., Zhu, M., Chen, K., Nie, X., Deng, Q., Hazlett, L. D., ... Huang, X. (2013). TREM-2 promotes host resistance against Pseudomonas aeruginosa infection by suppressing corneal inflammation via a PI3K/Akt signaling pathway. Investigative Ophthalmology & Visual Science, 54(5), pp. 3451-62. doi:10.1167/iovs.12-10938.
Sun M, et al. TREM-2 Promotes Host Resistance Against Pseudomonas Aeruginosa Infection By Suppressing Corneal Inflammation Via a PI3K/Akt Signaling Pathway. Invest Ophthalmol Vis Sci. 2013 May 17;54(5):3451-62. PubMed PMID: 23611998.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TREM-2 promotes host resistance against Pseudomonas aeruginosa infection by suppressing corneal inflammation via a PI3K/Akt signaling pathway. AU - Sun,Mingxia, AU - Zhu,Min, AU - Chen,Kang, AU - Nie,Xinxin, AU - Deng,Qiuchan, AU - Hazlett,Linda D, AU - Wu,Yongjian, AU - Li,Meiyu, AU - Wu,Minhao, AU - Huang,Xi, Y1 - 2013/05/17/ PY - 2013/4/25/entrez PY - 2013/4/25/pubmed PY - 2013/7/23/medline KW - bacteria KW - cornea KW - cytokines KW - inflammation SP - 3451 EP - 62 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 54 IS - 5 N2 - 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. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/23611998/TREM_2_promotes_host_resistance_against_Pseudomonas_aeruginosa_infection_by_suppressing_corneal_inflammation_via_a_PI3K/Akt_signaling_pathway_ L2 - http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.12-10938 DB - PRIME DP - Unbound Medicine ER -