GM-CSF can be secreted by multiple cell types, whereas IL-3 is mostly restricted to T cells, yet innate response activator (IRA) B cells, a subset of innate B1 B cells, also produce significant amounts of these cytokines during bacterial sepsis via Toll-like receptor 4 (TLR4)/MyD88 sensing of lipopolysaccharides.
The execution of shock following high dose E. coli lipopolysaccharide (LPS) or bacterial sepsis in mice required pro-apoptotic caspase-8 in addition to pro-pyroptotic caspase-11 and gasdermin D. Hematopoietic cells produced MyD88- and TRIF-dependent inflammatory cytokines sufficient to initiate shock without any contribution from caspase-8 or caspase-11.