Toll-like receptor 2 recognition of the microsporidia Encephalitozoon spp. induces nuclear translocation of NF-kappaB and subsequent inflammatory responses.

Abstract:

: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-kappaB, 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-kappaB 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-kappaB 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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Fischer J,Suire C,Hale-Donze H

doi

10.1128/IAI.00733-08

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

4737-44

issue

10

eissn

0019-9567

issn

1098-5522

pii

IAI.00733-08

journal_volume

76

pub_type

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