April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
TREM -1 Amplifies Corneal Inflammation After P. aeruginosa Infection by Modulating Th1-/Th2-Type Immune Response
Author Affiliations & Notes
  • X. Huang
    Anatomy & Cell Biology, Wayne State Univ Sch of Med, Detroit, Michigan
    Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
  • W. Du
    Anatomy & Cell Biology, Wayne State Univ Sch of Med, Detroit, Michigan
  • P. Zhang
    Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
  • K. Zhang
    Anatomy & Cell Biology, Wayne State Univ Sch of Med, Detroit, Michigan
  • M. Sun
    Anatomy & Cell Biology, Wayne State Univ Sch of Med, Detroit, Michigan
  • L. D. Hazlett
    Anatomy & Cell Biology, Wayne State Univ Sch of Med, Detroit, Michigan
  • R. P. Barrett
    Anatomy & Cell Biology, Wayne State Univ Sch of Med, Detroit, Michigan
  • Footnotes
    Commercial Relationships  X. Huang, None; W. Du, None; P. Zhang, None; K. Zhang, None; M. Sun, None; L.D. Hazlett, None; R.P. Barrett, None.
  • Footnotes
    Support  NIH R01 EY019021, NIH P30 EY04068 and NSFC U0832006.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3902. doi:https://doi.org/
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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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To elucidate the role of TREM-1 (Triggering receptors expressed on myeloid cells 1) in Pseudomonas aeruginosa (P. aeruginosa) keratitis.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: inflammation • keratitis • microbial pathogenesis: experimental studies 
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