Hemozoin-mediated inflammasome activation limits long-lived anti-malarial immunity.

ABSTRACT: During acute malaria, most individuals mount robust inflammatory responses that limit parasite burden. However, long-lived sterilizing anti-malarial memory responses are not efficiently induced, even following repeated Plasmodium exposures. Using multiple Plasmodium species, genetically modified parasites, and combinations of host genetic and pharmacologic approaches, we find that the deposition of the malarial pigment hemozoin directly limits the abundance and capacity of conventional type 1 dendritic cells to prime helper T cell responses. Hemozoin-induced dendritic cell dysfunction results in aberrant Plasmodium-specific CD4 T follicular helper cell differentiation, which constrains memory B cell and long-lived plasma cell formation. Mechanistically, we identify that dendritic cell-intr

SUBMITTER: Pack AD 

PROVIDER: S-EPMC8432597 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature