2007
DOI: 10.4049/jimmunol.178.2.1068
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Innate Immune Responses to Endosymbiotic Wolbachia Bacteria in Brugia malayi and Onchocerca volvulus Are Dependent on TLR2, TLR6, MyD88, and Mal, but Not TLR4, TRIF, or TRAM

Abstract: The discovery that endosymbiotic Wolbachia bacteria play an important role in the pathophysiology of diseases caused by filarial nematodes, including lymphatic filariasis and onchocerciasis (river blindness) has transformed our approach to these disabling diseases. Because these parasites infect hundreds of millions of individuals worldwide, understanding host factors involved in the pathogenesis of filarial-induced diseases is paramount. However, the role of early innate responses to filarial and Wolbachia li… Show more

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Cited by 106 publications
(103 citation statements)
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“…These adaptors mediate TLR signaling either alone or in combination with MyD88 and confer the specificity of TLR-mediated inflammatory responses. Recently, it has been shown that MyD88 and TIRAP are the primary adaptor molecules recruited during TLR stimulation by filarial products (12) and that MyD88 gene expression was significantly decreased in dendritic cells exposed to live filarial parasites (24). We examined the gene expression of the above-mentioned TLR adaptors but did not observe any significant difference in the expression of MyD88, TRAM, TRIF, TIRAP, or TRAF-6 at the mRNA level in response to TLR stimulation between the three groups.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…These adaptors mediate TLR signaling either alone or in combination with MyD88 and confer the specificity of TLR-mediated inflammatory responses. Recently, it has been shown that MyD88 and TIRAP are the primary adaptor molecules recruited during TLR stimulation by filarial products (12) and that MyD88 gene expression was significantly decreased in dendritic cells exposed to live filarial parasites (24). We examined the gene expression of the above-mentioned TLR adaptors but did not observe any significant difference in the expression of MyD88, TRAM, TRIF, TIRAP, or TRAF-6 at the mRNA level in response to TLR stimulation between the three groups.…”
Section: Discussionmentioning
confidence: 99%
“…Upon binding to their cognate ligands, TLRs activate the innate immune response, leading to the production of proinflammatory cytokines and chemokines (13). Studies of animal models of filarial infection and in vitro studies in humans have suggested that Wolbachia-derived molecules from filarial parasites are key inducers of proinflammatory cytokines (7,12,27,28). Moreover, this inflammatory response to Wolbachia has been shown to be mediated primarily through TLR2, TLR4, and TLR6.…”
mentioning
confidence: 99%
“…Recognition of Wolbachia products on macrophages and DCs is mediated by TLR2/TLR6, leading to MyD88/TIRAP activation and the release of pro-inflammatory cytokines via NF-kB. 110 Previous work suggests that Th2 immune responses predominate (see Pearlman and Hall 111 for review), but Turner et al 112 showed that activated CD11c + DCs upregulate CD80 and CD86 adhesion molecules and can stimulate a CD4 + T-cell activation with a predominantly Th1 response. Interestingly, this study also demonstrated that Wolbachia depletion resulted in a switch to a Th2-driven inflammatory response.…”
Section: Onchocerca Volvulus (Onchocerciasis) Onchocerciasis Is Due Tmentioning
confidence: 99%
“…These endosymbiotic organisms, which have been shown to be released along with microfilariae by mature worms or by dying microfilariae, induce proinflammatory immune responses (11,17). Further, the Wolbachia surface protein WSP has been shown to induce IL-12 production by acting through TLR2 and -4 (4, 5).…”
Section: Vol 76 2008 Sepsis In Helminth-infected Mice 1673mentioning
confidence: 99%