Spotted fever group Rickettsia infection kinetics and cutaneous host response during single tick feeding events

Rickettsia parkeri, an emerging tick-borne pathogen, is transmitted by Amblyomma maculatum. Initial bacterial inoculation occurs in the skin via infected tick bite. During blood acquisition, tick salivary factors manipulate host hemostatic and immune responses. Examination of rickettsial pathogenesis and the host response to infection in murine models primarily utilize needle inoculation. As a result, biological variables including transmission dynamics and the influence of vector saliva on the host response at the infection site are undefined. To test the hypothesis that a distinct host cutaneous immune response will be elicited based on the infection status of the tick, a single tick feeding model was developed to assess the transmission and dissemination kinetics of R. parkeri from the early stage of tick attachment (1 hour) to late feeding stage (144 hours). Furthermore, changes in the cutaneous immune response were characterized through immunophenotyping, cytokine and chemokine profiling, and histopathological analysis. The data show that transmission of R. parkeri from the infected tick to the host occurs within 1 hour-post tick attachment (hpa), with rapid dissemination to lymph nodes and internal tissues. The quantifiable bacterial load in the mouse skin delivered by an infected tick was 9,500 bacteria at 3 hours, increasing to 15,000 and 22,000 rickettsiae at 48 and 144 hours, respectively. Independent of tick infection status, the degree of time-dependent inflammation was similar at 3 and 48 hpa. However, in R. parkeri-infected skin at 144 hpa, macrophages were the dominant cell type, with enhanced levels of IFN-γ and TNF-α while IL-10 production was reduced. The data suggest delayed pro-inflammatory activation in response to rickettsial infection when delivered by ticks. This study yields valuable insights into the early events of Rickettsia transmission and the host response, providing the basis for the development of preventive strategies against tick-borne rickettsial disease.