title: Inhibition of TREM-1 and Dectin-1 Alleviates the Severity of Fungal Keratitis by Modulating Innate Immune Responses.
abstract: OBJECTIVE
  To explore the possibility that inhibiting triggering receptor expressed on myeloid cells-1 (TREM-1) and Dendritic cell-associated C-type lectin-1(Dectin-1) could modulate the innate immune response and alleviate the severity of corneal fungal keratitis.
  
  
  METHODS
  TREM-1 and Dectin-1 expression was detected in fungus-infected human corneal specimens by real-time PCR. C57BL/6 (B6) mice were injected with Aspergillus fumigatus and divided into 4 groups that received subconjunctival injections of PBS and IgG as a control (group I), mTREM-1/IgG fusion protein (group II), the soluble β-glucan antagonist laminarin (group III), or mTREM-1/Fc and laminarin (group IV). Corneal virulence was evaluated based on clinical scores. TREM-1 and Dectin-1 mRNA levels were assayed using real-time PCR. The distribution patterns of TREM-1, Dectin-1 and cellular infiltrates in fungus-infected corneas were examined by immunohistochemistry. Moreover, changes in T Helper Type1 (Th1)-/ T Helper Type1 (Th2)- type cytokines and proinflammatory cytokines were measured.
  
  
  RESULTS
  The expression of TREM-1 and Dectin-1 increased significantly and correlated positively with the progression of fungal keratitis. Most infiltrated cells were neutrophils and secondarily macrophages in infected cornea. The clinical scores decreased after interfering with TREM-1 and Dectin-1 expression in infected mouse corneas. Levels of Th1-type cytokines including interleukin-12 (IL-12), IL-18 and interferon-γ (IFN-γ) were decreased in the cornea, while the levels of Th2-type cytokines, including IL-4, IL-5 and IL-10, showed obvious increases.
  
  
  CONCLUSIONS
  TREM-1 and Dectin-1 function concurrently in the corneal innate immune response by regulating inflammatory cytokine expression in fungal keratitis. Inhibition of TREM-1 and Dectin-1 can alleviate the severity of corneal damage by downregulating the excessive inflammatory response.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, 510064, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, 510064, China.
authors.forename: Weilan
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Immunology, Institute of Human virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.|Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China.
authors.forename: Qiuchan
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Department of Immunology, Institute of Human virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.|Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China.
authors.forename: Minhao
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Huaili
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, 510064, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, 510064, China.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, 510064, China.|Department of Immunology, Institute of Human virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.|Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, 510064, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yuan
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001228:Aspergillosis / Q000276:immunology / Q000473:pathology; D001232:Aspergillus fumigatus / Q000276:immunology*; D003315:Cornea / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007634:Keratitis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology; D051379:Mice; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; C546929:CLEC7A protein, human; D000099181:Dectin-1; C408842:TREM1 protein, human; C517262:TREM1 protein, mouse