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Infect. Immun. doi:10.1128/IAI.00733-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

TLR2 recognition of the microsporidia Encephalitozoon spp. induces nuclear translocation of NF-B and subsequent inflammatory responses

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

^* To whom correspondence should be addressed. Email: hhaled1{at}lsu.edu.

	Abstract

Microsporidia are obligate intracellular parasites that are ubiquitous in nature and have been recognized as 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. These are the first demonstrations of host receptor recognition of any species of microsporidian. TLR2 ligation is known to activate NF-B resulting in inflammatory cytokines such as TNF- and IL-8. We found that the infection of primary human macrophages leads to the nuclear translocation of NF-B as early as 1 hr and the subsequent production of TNF- 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 macrophage using siRNA. This knock-down resulted in decreases in both nuclear translocation of NF-B and the levels of TNF- 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.