TREM-1 amplifies corneal inflammation after Pseudomonas aeruginosa infection by modulating Toll-like receptor signaling and Th1/Th2-type immune responses.

Abstract

As a novel family of cell surface receptors, triggering receptors expressed on myeloid cells (TREMs) play an important role in inflammatory responses. However, the role of TREMs in the ocular immune system remains unknown. In this study, we examined the expression and function of TREM-1 in Pseudomonas aeruginosa keratitis, one of the most common sight-threatening ocular diseases. TREM-1 was significantly increased in human corneas after P. aeruginosa infection. Consistent with TREM-1 expression at the human ocular surface, TREM-1 levels (mRNA and protein) were also elevated in the infected corneas of C57BL/6 (B6) mice at 1, 3, and 5 days postinfection. To determine whether TREM-1 dictates the outcome of P. aeruginosa keratitis in susceptible mice, TREM-1 signaling in B6 mice was blocked with a soluble mTREM-1/Fc fusion protein. The results indicated that blockade of TREM-1 reduced the severity of corneal disease, polymorphonuclear neutrophil infiltration, Th1/proinflammatory cytokine expression and Toll-like receptor (TLR) activation but enhanced the production of Th2 cytokines, murine β-defensin 2 (mBD2), single Ig interleukin-1R-related molecule (SIGIRR), and ST2. Furthermore, we also used agonistic anti-mTREM-1 antibody to activate TREM-1 signaling in B6 mice and found that TREM-1 activation resulted in worsened disease and earlier corneal perforation in infected B6 mouse corneas and elevated production of proinflammatory cytokines and TLR signaling molecules but reduced expression of mBD2, SIGIRR, and ST2. To the best of our knowledge, this study provides the first evidence that TREM-1 functions as an inflammatory amplifier in P. aeruginosa keratitis by modulating TLR signaling and Th1/Th2 responses.

• Authors: Minhao Wu, Anping Peng, Mingxia Sun, Qiuchan Deng, Linda D Hazlett, Jin Yuan, Xialin Liu, Qianying Gao, Lianqiang Feng, Junfang He, Ping Zhang, Xi Huang
• Journal: Infection and immunity (Infect Immun) Vol. 79 Issue 7 Pg. 2709-16 (Jul 2011) ISSN: 1098-5522 [Electronic] United States
• PMID: 21555403 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Cytokines
• Il1rl1 protein, mouse
• Interleukin-1 Receptor-Like 1 Protein
• Membrane Glycoproteins
• Receptors, Immunologic
• Receptors, Interleukin
• Receptors, Interleukin-1
• Recombinant Fusion Proteins
• SIGIRR protein, mouse
• TREM1 protein, human
• TREM1 protein, mouse
• Toll-Like Receptors
• Triggering Receptor Expressed on Myeloid Cells-1
• beta-Defensins

Topics

• Adult
• Aged
• Animals
• Antibodies
• Cornea (immunology, metabolism)
• Cytokines (biosynthesis, metabolism)
• Eye Infections, Bacterial (genetics, immunology, metabolism)
• Female
• Humans
• Interleukin-1 Receptor-Like 1 Protein
• Keratitis (immunology, metabolism, microbiology)
• Male
• Membrane Glycoproteins (immunology, metabolism)
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Neutrophil Infiltration
• Neutrophils (immunology)
• Pseudomonas Infections (genetics, immunology, metabolism)
• Pseudomonas aeruginosa (genetics, immunology, metabolism)
• Receptors, Immunologic (immunology, metabolism)
• Receptors, Interleukin (biosynthesis)
• Receptors, Interleukin-1 (biosynthesis)
• Recombinant Fusion Proteins (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Th1 Cells (immunology)
• Th2 Cells (immunology)
• Toll-Like Receptors (immunology, metabolism)
• Triggering Receptor Expressed on Myeloid Cells-1
• beta-Defensins (biosynthesis)