MyD88-Dependent Signaling Contributes to Host Defense against Ehrlichial Infection

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MyD88-Dependent Signaling Contributes to Host Defense against Ehrlichial Infection

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dc.contributor.author Koh, Young-Sang
dc.contributor.author Koo, Jung-Eun
dc.contributor.author Biswas, Amlan
dc.contributor.author Kobayashi, Koichi S
dc.date.accessioned 2011-03-23T16:59:29Z
dc.date.issued 2010
dc.identifier.citation Koh, Young-Sang, Jung-Eun Koo, Amlan Biswas, and Koichi S. Kobayashi. 2010. MyD88-Dependent signaling contributes to host defense against ehrlichial infection. PLoS ONE 5(7): e11758. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4768917
dc.description.abstract The ehrlichiae are small Gram-negative obligate intracellular bacteria in the family Anaplasmataceae. Ehrlichial infection in an accidental host may result in fatal diseases such as human monocytotropic ehrlichiosis, an emerging, tick-borne disease. Although the role of adaptive immune responses in the protection against ehrlichiosis has been well studied, the mechanism by which the innate immune system is activated is not fully understood. Using Ehrlichia muris as a model organism, we show here that MyD88-dependent signaling pathways play a pivotal role in the host defense against ehrlichial infection. Upon E. muris infection, MyD88-deficient mice had significantly impaired clearance of E. muris, as well as decreased inflammation, characterized by reduced splenomegaly and recruitment of macrophages and neutrophils. Furthermore, MyD88-deficient mice produced markedly lower levels of IL-12, which correlated well with an impaired Th1 immune response. In vitro, dendritic cells, but not macrophages, efficiently produced IL-12 upon E. muris infection through a MyD88-dependent mechanism. Therefore, MyD88-dependent signaling is required for controlling ehrlichial infection by playing an essential role in the immediate activation of the innate immune system and inflammatory cytokine production, as well as in the activation of the adaptive immune system at a later stage by providing for optimal Th1 immune responses. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0011758 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909256/pdf/ en_US
dash.license LAA
dc.subject immunology en_US
dc.subject immunity to infections en_US
dc.subject innate immunity en_US
dc.subject microbiology en_US
dc.title MyD88-Dependent Signaling Contributes to Host Defense against Ehrlichial Infection en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Biswas, Amlan
dc.date.available 2011-03-23T16:59:29Z
dash.affiliation.other HMS^Pathology en_US
dash.affiliation.other HMS^Pathology en_US

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