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Infection and Immunity, October 2008, p. 4737-4744, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.00733-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Toll-Like Receptor 2 Recognition of the Microsporidia Encephalitozoon spp. Induces Nuclear Translocation of NF-{kappa}B and Subsequent Inflammatory Responses{triangledown}

Jeffrey Fischer, Colby Suire,{dagger} and Hollie Hale-Donze*

Louisiana State University, Department of Biological Sciences, 202 Life Sciences Building, Baton Rouge, Louisiana 70803

Received 10 June 2008/ Returned for modification 12 July 2008/ Accepted 29 July 2008

Microsporidia are obligate intracellular parasites that are ubiquitous in nature and have been recognized as causing an important emerging disease among immunocompromised individuals. Limited knowledge exists about the immune response against these organisms, and virtually nothing is known about the receptors involved in host recognition. Toll-like receptors (TLR) are pattern recognition receptors that bind to specific molecules found on pathogens and signal a variety of inflammatory responses. In this study, we show that both Encephalitozoon cuniculi and Encephalitozoon intestinalis are preferentially recognized by TLR2 and not by TLR4 in primary human macrophages. This is the first demonstration of host receptor recognition of any microsporidian species. TLR2 ligation is known to activate NF-{kappa}B, resulting in inflammatory cytokines, such as tumor necrosis factor alpha (TNF-{alpha}) and interleukin-8 (IL-8). We found that the infection of primary human macrophages leads to the nuclear translocation of NF-{kappa}B in as early as 1 h and the subsequent production of TNF-{alpha} and IL-8. To verify the direct role of TLR2 parasite recognition in the production of these cytokines, the receptor was knocked down in primary human macrophages using small interfering RNA. This knockdown resulted in decreases in both the nuclear translocation of NF-{kappa}B and the levels of TNF-{alpha} and IL-8 after challenge with spores. Taken together, these experiments directly link the initial inflammatory response induced by Encephalitozoon spp. to TLR2 stimulation in human macrophages.

* Corresponding author. Mailing address: Louisiana State University, Department of Biological Sciences, 202 Life Sciences Building, Baton Rouge, LA 70803. Phone: (225) 578-4053. Fax: (225) 578-2597. E-mail address:hhaled1{at}lsu.edu

{triangledown} Published ahead of print on 4 August 2008.

Editor: W. A. Petri, Jr.

{dagger} Present address: University of Texas M. D. Anderson Cancer Center, Department of Cancer Genetics, 1515 Holcombe Blvd., Houston, TX 77030.

Infection and Immunity, October 2008, p. 4737-4744, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.00733-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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