Defining how Antibiotic Treatments shape Host Immunity

Abstract Although antibiotics are clinically crucial, little is known about how they impact a patient’s immune response to infection. We address that gap by investigating macrophages respond bacteria treated with different classes of antibiotics. broadly susceptible E. coli strain 8 separate antibiotics, infected macrophages, and compared much TNF the various antibiotic-treated elicited from macrophages. found cidal (that kill bacteria) ~2–3 fold more than equivalent amounts bacteriostatic (growth limiting) A panel 12 clinical isolates patients (4 each E.coli, Enterobacter Klebsiella) showed similar pattern antibiotic class-dependent inflammatory cytokine output. then evaluated an in vivo IP injection model pre-treated bacteria, heat-killed or vehicle alone. At two hr post infection, we saw ~35–200% increases serum levels pro-inflammatory cytokines induced cidal-treated static-treated bacteria. Consistent prior data, both killed no cytokines. Preliminary imaging data suggest treatment drugs causes most dead form large aggregates, while static does not. now aim clarify role these aggregates driving this outcome. This may identify additional patterns responses could guide development improved antimicrobial strategies. work supported Intramural Research Program NIAID, NIH. Supported