Dynamic contributions of 3 distinct populations of PMNs constitute the innate immune response to S aureus infection. (A) A model depicting the dynamic feedback between the bone marrow compartment and the wound compartment during bacterial infection. Local S aureus infection triggers signals (eg, hematopoietic cytokines) to maintain an enhanced number of PMNs in infected tissue. This can be largely achieved by increased production and mobilization of PMNs in the bone marrow and their recruitment into local infected tissue, where their lifespan is markedly extended to provide sustained immune protection. In addition, bone marrow c-kit⁺-progenitor expansion and mobilization are activated by S aureus. Progenitor cells infiltrate the site of infection, where they proliferate and differentiate into functional PMNs in part via a MyD88-dependent mechanism to provide additional immune protection. P_influx represents the number of newly infiltrated PMNs from the blood to the infected tissue during a S aureus infection; P_ckit, the number of newly produced PMNs in the tissue by proliferation of c-kit progenitors; and P_survival, the number of early recruited PMNs that persist after day 1 of infection within the wound. (B) Relative contribution of enhanced PMN survival and their local production by tissue-infiltrated c-kit⁺ cells that contribute in equal proportion by day 3 to maintain tissue PMN number during S aureus infection. Mathematical modeling predicts the relative contributions of each compartment between days 1 and 5 of S aureus infection (1 × 10⁷ CFUs; for details, see supplemental Methods).