title: Toll-like receptor 2 regulates CXC chemokine production and neutrophil recruitment to the cornea in Onchocerca volvulus/Wolbachia-induced keratitis.
abstract: The filarial nematode Onchocerca volvulus is the causative organism of river blindness. Our previous studies demonstrated an essential role for endosymbiotic Wolbachia bacteria in corneal disease, which is characterized by neutrophil infiltration into the corneal stroma and the development of corneal haze. To determine the role of Toll-like receptors (TLRs) in neutrophil recruitment and activation, we injected a soluble extract of O. volvulus containing Wolbachia bacteria into the corneal stromata of C57BL/6, TLR2-/-, TLR4-/-, TLR2/4-/-, and TLR9-/- mice. We found an essential role for TLR2, but not TLR4 or TLR9, in neutrophil recruitment to the cornea and development of corneal haze. Furthermore, chimeric mouse bone marrow studies showed that resident bone marrow-derived cells in the cornea can initiate this response. TLR2 expression was also essential for CXC chemokine production by resident cells in the cornea, including corneal fibroblasts, and for neutrophil activation. Taken together, these findings indicate that Wolbachia activates TLR2 on resident bone marrow-derived cells in the corneal stroma to produce CXC chemokines, leading to neutrophil recruitment to the corneal stroma, and that TLR2 mediates O. volvulus/Wolbachia-induced neutrophil activation and development of corneal haze.
authors: Department of Ophthalmology, Case Western Reserve University, Cleveland, OH 44106-7286, USA.
authors: Illona
authors: I
authors: Gillette-Ferguson
authors: Katrin
authors: K
authors: Daehnel
authors: Amy G
authors: AG
authors: Hise
authors: Yan
authors: Y
authors: Sun
authors: Eric
authors: E
authors: Carlson
authors: Eugenia
authors: E
authors: Diaconu
authors: Helen F
authors: HF
authors: McGarry
authors: Mark J
authors: MJ
authors: Taylor
authors: Eric
authors: E
authors: Pearlman
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002460:Cell Line; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000276:immunology*; D003315:Cornea / Q000276:immunology / Q000473:pathology; D005260:Female; D007634:Keratitis / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D017181:Onchocerca volvulus / Q000276:immunology*; D015827:Onchocerciasis, Ocular / Q000276:immunology* / Q000469:parasitology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D020577:Wolbachia / Q000276:immunology*
chemical_list: D019743:Chemokines, CXC; D051195:Toll-Like Receptor 2