Amblyomma maculatum Immunomodulation in Mammalian Models of Rickettsia parkeri Rickettsiosis

Rickettsia parkeri is an emerging human pathogen and spotted fever group Rickettsia that is transmitted via Amblyomma maculatum (the Gulf Coast tick) in the United States. Since these ticks must feed for several days in order to molt to the next life cycle, they must be able to counteract the host immune response. Despite this fact, there have been few studies that evaluate the immunomodulatory effect of this vector and the resultant influence on rickettsial disease. The hypothesis of this research is that, if A. maculatum feeding modifies the host immune response, this immunomodulation will enhance disease caused by R. parkeri. In order to assess this interaction in vivo, rhesus macaques were used to compare intradermal needle inoculation of R. parkeri alone to inoculation during A. maculatum feeding and A. maculatum feeding alone. Tick feeding enhanced local disease and the systemic inflammatory response induced by R. parkeri, resulting in increased rickettsial dissemination early in infection, and increased persistence at the inoculation site. In order to quantify the role of A. maculatum on the acute rickettsial immune response, C3H/HeN mice were intradermally inoculated with R. parkeri both alone and in the presence of A. maculatum saliva. The cellular influx of neutrophils and macrophages was significantly downregulated in the R. parkeri + saliva group as compared to R. parkeri inoculation alone. However, rickettsial load and the cutaneous cytokine response were not significantly modified by A. maculatum saliva. Taken together these studies indicate that A. maculatum feeding enhances cutaneous pathology in R. parkeri rickettsiosis despite the fact that tick saliva inhibits the acute cutaneous cellular infiltrate. Therefore, the immunomodulatory properties of tick feeding cannot be attributed to just the inoculation of saliva alone by the ticks. Future study should evaluate the overall impact of these effects on the establishment of rickettsiosis in the mammalian host in order to develop novel anti-transmission therapeutics