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UID:20260806T142218EDT-0086lHMHg5@132.216.98.100
DTSTAMP:20260806T182218Z
DESCRIPTION:\nToll-like receptors (TLRs) play important roles in sensing an
 d\ndirecting immune responses to viral and microbial pathogens. We\nexamin
 ed the mechanism by which TLRs contribute to host defense\nagainst the let
 hal intracellular pathogens Toxoplasma gondii and\nFrancisella tularensis 
 by using mice selectively lacking the key\nTLR signaling protein MyD88 in 
 different innate immune cell types.\nLack of MyD88 in dendritic cells (DCs
 )\, but not in macrophages or\nneutrophils\, resulted in high susceptibili
 ty to infection with T.\ngondii. In the mice deficient in MyD88 in DCs\, t
 he early IL-12\nresponse by DCs was ablated\, the IFN-g response by natura
 l killer\ncells was delayed\, and the recruited inflammatory monocytes wer
 e\nincapable of killing the T. gondii parasites. The T cell response\,\nal
 though attenuated in these mice\, was sufficient to eradicate the\nparasit
 e during the chronic stage\, provided that defects in DC\nactivation were 
 compensated by IL-12 treatment. These results\ndemonstrate an unappreciate
 d central role of DCs in orchestrating\nthe innate immune response to an i
 ntracellular parasite and\nestablish that defects in pathogen recognition 
 by DCs predetermine\nsensitivity to infection. A remarkable corollary of o
 ur findings is\nthat the innate recognition of T. pathogens by DCs predete
 rmines\nthe outcome of the chronic phase of the infection independently of
 \nthe status of T cell activation. That is\, if the type 1 innate\nimmunit
 y fails to contain the infection adequately while adaptive\nimmunity is be
 ing induced\, the resulting greater burden of\nparasites cannot be adequat
 ely controlled by T cell immunity\nwithout lethality in the chronic phase.
 \nA similar defensive pathway also appeared to be employed against\nthe in
 tracellular bacterial pathogen Francisella tularensis\,\nsuggesting a gene
 ral role for TLR signaling in DC for regulation of\ninnate immune response
 s to intracellular pathogens.\n
DTSTART:20101129T203000Z
DTEND:20101129T213000Z
LOCATION:McIntyre Medical Building\, CA\, QC\, Montreal\, H3G 1Y6\, 3655 pr
 omenade Sir William Osler
SUMMARY:Guest Speaker\, Dr. Felix Yarovinsky-Excellence in Genetics & Immun
 ology Seminar Series
URL:/channels/event/guest-speaker-dr-felix-yarovinsky-
 excellence-genetics-immunology-seminar-series-169661
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