Toll-like receptor 2 regulates CXC chemokine production and neutrophil recruitment to the cornea in Onchocerca volvulus/Wolbachia-induced keratitis

Gillette-Ferguson, I., Daehnel, K., Hise, A. G., Sun, Y., Carlson, E., Diaconu, E., McGarry, Helen F., Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275 and Pearlman, E. (2007) 'Toll-like receptor 2 regulates CXC chemokine production and neutrophil recruitment to the cornea in Onchocerca volvulus/Wolbachia-induced keratitis'. Infection and Immunity, Vol 75, Issue 12, pp. 5908-5915.

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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.

Item Type:	Article
Uncontrolled Keywords:	endosymbiotic wolbachia-bacteria toll-like receptor myeloid differentiation factor-88 endotoxin-induced keratitis river-blindness brugia-malayi filarial nematodes surface protein immune-responses dendritic cells
Subjects:	WC Communicable Diseases > Tropical and Parasitic Diseases > WC 885 Onchocerciasis WW Ophthalmology > Diseases. Color Perception > WW 160 Eye infections. Hypersensitivity diseases (General or not elsewhere classified)
Faculty: Department:	Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI):	https://doi.org/10.1128/IAI.00991-07
Depositing User:	Mary Creegan
Date Deposited:	17 Sep 2010 08:57
Last Modified:	16 Sep 2019 09:00
URI:	https://archive.lstmed.ac.uk/id/eprint/1198

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