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Infection and Immunity, December 2007, p. 5908-5915, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.00991-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Toll-Like Receptor 2 Regulates CXC Chemokine Production and Neutrophil Recruitment to the Cornea in Onchocerca volvulus/ Wolbachia-Induced Keratitis{triangledown}

Illona Gillette-Ferguson,1,{dagger} Katrin Daehnel,1,{dagger} Amy G. Hise,2 Yan Sun,1 Eric Carlson,1 Eugenia Diaconu,1 Helen F. McGarry,3 Mark J. Taylor,3 and Eric Pearlman1,2*

Department of Ophthalmology,1 the Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio,2 Filariasis Research Laboratory, Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kindgom3

Received 19 July 2007/ Returned for modification 20 August 2007/ Accepted 31 August 2007

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.

* Corresponding author. Mailing address: Department of Ophthalmology and Center for Global Health and Diseases, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-7286. Phone: (216) 368-1856. Fax: (216) 368-4825. E-mail: Eric.Pearlman{at}case.edu

{triangledown} Published ahead of print on 17 September 2007.

Editor: W. A. Petri, Jr.

{dagger} I.G.-F. and K.D. contributed equally to the work presented in the manuscript.

Infection and Immunity, December 2007, p. 5908-5915, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.00991-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Turner, J. D., Langley, R. S., Johnston, K. L., Gentil, K., Ford, L., Wu, B., Graham, M., Sharpley, F., Slatko, B., Pearlman, E., Taylor, M. J. (2009). Wolbachia Lipoprotein Stimulates Innate and Adaptive Immunity through Toll-like Receptors 2 and 6 to Induce Disease Manifestations of Filariasis. J. Biol. Chem. 284: 22364-22378 [Abstract] [Full Text]  
  • Gentil, K., Pearlman, E. (2009). Gamma Interferon and Interleukin-1 Receptor 1 Regulate Neutrophil Recruitment to the Corneal Stroma in a Murine Model of Onchocerca volvulus Keratitis. Infect. Immun. 77: 1606-1612 [Abstract] [Full Text]  


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