Shielded by the dead: how killed bacteria shape the dynamics and evolution of innate immunity.

The outcome of an infection is determined by the dynamic interplay between microbial growth and host immunity. During a bacterial infection, bacteria killed by innate immune effectors can accumulate as corpses in the extracelluar space, where they can continue to bind (and thus sequester) immune effectors. The impacts on infection outcomes of continued biochemical activity ("sponginess") by the dead have been generally overlooked in theoretical and empirical studies of within-host disease dynamics. We develop a mechanism-based mathematical model of within-host dynamics that incorporates host microbial sensing, the production of immune effectors, the interaction of those effectors with microbes, and shutdown of the immune response after an infection has been controlled. Corpse sponginess impedes the host's ability to control infection, but at the same time, the rapid mopping up of effectors by bacterial corpses also protects host tissue against autoimmune self-harm from immune effectors still circulating after the infection has been resolved. This dual impact of bacterial sponginess alters the trade-off between damage done by infecting bacteria versus autoimmune damage, consequently shifting the evolutionarily optimal immune activation and shutdown kinetics. Thus, the sponginess of bacterial corpses likely shapes both short-term infection dynamics and the long-term evolution of immune systems.