Abstract
Rickettsia parkeri is an emerging eschar-causing human pathogen in the spotted fever group of Rickettsia and is transmitted by the Gulf coast tick, Amblyomma maculatum. Tick saliva has been shown to alter both the cellular and humoral components of the innate and adaptive immune systems. However, the effect of this immunomodulation on Rickettsia transmission and pathology in an immunocompetent vertebrate host has not been fully examined. We hypothesize that, by modifying the host immune response, tick feeding enhances infection and pathology of pathogenic spotted fever group Rickettsia sp. In order to assess this interaction in vivo, a pilot study was conducted using five rhesus macaques that were divided into three groups. One group was intradermally inoculated with low passage R. parkeri (Portsmouth strain) alone (n = 2) and another group was inoculated during infestation by adult, R. parkeri-free A. maculatum (n = 2). The final macaque was infested with ticks alone (tick feeding control group). Blood, lymph node and skin biopsies were collected at several time points post-inoculation/infestation to assess pathology and quantify rickettsial DNA. As opposed to the tick-only animal, all Rickettsia-inoculated macaques developed inflammatory leukograms, elevated C-reactive protein concentrations, and elevated TH1 (interferon-γ, interleukin-15) and acute phase inflammatory cytokines (interleukin-6) post-inoculation, with greater neutrophilia and interleukin-6 concentrations in the tick plus R. parkeri group. While eschars formed at all R. parkeri inoculation sites, larger and slower healing eschars were observed in the tick feeding plus R. parkeri group. Furthermore, dissemination of R. parkeri to draining lymph nodes early in infection and increased persistence at the inoculation site were observed in the tick plus R. parkeri group. This study indicates that rhesus macaques can be used to model R. parkeri rickettsiosis, and suggests that immunomodulatory factors introduced during tick feeding may enhance the pathogenicity of spotted fever group Rickettsia.
Highlights
Within the past fifteen years, there has been a more than a four-fold increase in the number of tick-borne rickettsial disease cases in humans in the United States [1,2]
The route of rickettsial inoculation used in this study, intradermal inoculation during tick feeding, while not replicating natural tick transmission of R. parkeri, was chosen in order to evaluate the effect of tick feeding on rickettsial pathogenesis as compared to the same dose of R. parkeri inoculated alone
Moderate to marked elevations in C-reactive protein (CRP) concentration, a major acute phase protein in rhesus macaques [45], and IL-6 concentration were noted during the same time frame
Summary
Within the past fifteen years, there has been a more than a four-fold increase in the number of tick-borne rickettsial disease cases in humans in the United States [1,2] During this time frame, Rickettsia parkeri, a member of the spotted fever group (SFG) of Rickettsia transmitted by Amblyomma maculatum (the Gulf coast tick), was first identified as a human pathogen [3] with several cases reported in North and South America [4,5,6,7,8,9,10]. An R. parkeri-associated eschar is a 0.5–2 cm in diameter, crusted, non-pruritic ulcer, surrounded by an indurated, erythematous halo. These lesions are characterized histologically by extensive necrosis of the epidermis and superficial dermis and prominent lymphohistiocytic vasculitis of dermal vessels [3,5,6,10]
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