This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Anthrax poses a clear and present danger as an agent of biological terrorism. The major virulence factor of Bacillus anthracis is the anthrax toxin, which comprises 3 subunits: protective antigen (PA), edema factor (EF) and lethal factor (LF). LF and PA together form a toxin known as lethal toxin (LT), which appears to play exquisitely different immunomodulatory roles, depending on the dose of toxin used. The effects of LT on dendritic cells (DCs), the most efficient antigen-presenting cells in the body, are not known. These mechanisms and their pathophysiological relevance will be investigated in the following aims:
Aim 1 : To determine the effect of LT on routine DC,function and adaptive immunity.
Aim 2 : To determine the effect of LT on murine DC function and adaptive immunity.
Aim 3 : To determine the effect of LT on distinct human DC subsets and adaptive immunity.
Aim 4 : To determine the pathophysiological relevance of LT-induced suppression during B.anthracis infection. Thus, the overall goal of this proposal is to acquire a deeper, mechanistic understanding of anthrax pathogenesis, and to use this knowledge to devise novel therapeutic modalities, which may be optimally effective at different stages of the infection.
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