FIG. 4.

Innate immunity as a driving force for B. burgdorferi heterogeneity during superinfection. (A) Innate immunity of a persistently infected mouse host blocks (“T” [horizontal] end of the line) secondary-infecting spirochetes that are homologous to initial-infecting B. burgdorferi. (B) Immune pressure mediated by the host innate response acts as a driving force for selection of heterologous B. burgdorferi. (C) In turn, only heterologous B. burgdorferi have the capacity to overcome this innate barrier (arrow end of the line) and establish superinfection. (D) and (E) Initially, VlsE is uninvolved in this selection process. However, variable VlsE is required for evasion of the host-acquired immune response that leads to persistent B. burgdorferi superinfection. Established persistence of secondary-infecting B. burgdorferi in the reservoir host increases the likelihood of transmitting a selected B. burgdorferi heterogeneity to seasonally available questing ticks (reprinted with permission form the American Society for Microbiology, Copyright 2014).³⁹