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
Authors
Hise, Amy G.Daehnel, Katrin
Gillette-Ferguson, Illona
Cho, Eun
McGarry, Helen F.
Taylor, Mark J.
Golenbock, Douglas T.
Fitzgerald, Katherine A.
Kazura, James W.
Pearlman, Eric
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2007-01-05Keywords
Adaptor Proteins, Vesicular TransportAnimals
Brugia malayi
Cell Line
Humans
Immunity, Innate
Inflammation
Interleukin-6
Macrophages
Membrane Transport Proteins
Mice
Mice, Inbred C57BL
Myelin Proteins
Myeloid Differentiation Factor 88
Onchocerca volvulus
Proteolipids
Receptors, Interleukin
Rickettsiaceae Infections
Symbiosis
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptor 6
Toll-Like Receptors
Tumor Necrosis Factor-alpha
Wolbachia
Wuchereria
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
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 ligands in the development of filarial diseases has not been fully elucidated. To determine the role of TLRs, we used cell lines transfected with human TLRs and macrophages from TLR and adaptor molecule-deficient mice and evaluated macrophage recruitment in vivo. Extracts of Brugia malayi and Onchocerca volvulus, which contain Wolbachia, directly stimulated human embryonic kidney cells expressing TLR2, but not TLR3 or TLR4. Wolbachia containing filarial extracts stimulated cytokine production in macrophages from C57BL/6 and TLR4(-/-) mice, but not from TLR2(-/-) or TLR6(-/-) mice. Similarly, macrophages from mice deficient in adaptor molecules Toll/IL-1R domain-containing adaptor-inducing IFN-beta and Toll/IL-1R domain-containing adaptor-inducing IFN-beta-related adaptor molecule produced equivalent cytokines as wild-type cells, whereas responses were absent in macrophages from MyD88(-/-) and Toll/IL-1R domain-containing adaptor protein (TIRAP)/MyD88 adaptor-like (Mal) deficient mice. Isolated Wolbachia bacteria demonstrated similar TLR and adaptor molecule requirements. In vivo, macrophage migration to the cornea in response to filarial extracts containing Wolbachia was dependent on TLR2 but not TLR4. These results establish that the innate inflammatory pathways activated by endosymbiotic Wolbachia in B. malayi and O. volvulus filaria are dependent on TLR2-TLR6 interactions and are mediated by adaptor molecules MyD88 and TIRAP/Mal.Source
J Immunol. 2007 Jan 15;178(2):1068-76.Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34897PubMed ID
17202370Related Resources
Link to Article in PubMedCollections
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