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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

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    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 Immunology
    Document Type
    Journal Article
    Publication Date
    2007-01-05
    Keywords
    Adaptor Proteins, Vesicular Transport
    Animals
    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
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    Link to Full Text
    http://www.jimmunol.org/content/178/2/1068.full.pdf+html
    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 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/20.500.14038/34897
    PubMed ID
    17202370
    Related Resources
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