Vector-pathogen-host interaction and immunopathogenesis of disease progression

National Institute Of Allergy And Infectious Diseases

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Abstract

The Vector-Pathogen-Host Interaction Unit (VPHIU) is interested in understanding the immune signaling involved in vector transmission of pathogens, primarily focusing on tissue-specific innate host responses induced by ehrlichial and rickettsial diseases. We believe that this initial response, at the skin site of the tick-pathogen interaction with the host, is associated with disease development and progression to severe outcome. Our in vivo murine model of ehrlichiosis, using the natural mode of infection by tick transmission, results in increased bacterial replication and dissemination throughout the body and more severe outcome, compared to intradermal needle injection of ehrlichiae (Saito and Walker, 2015). The dermal reaction to tick inoculation of the ehrlichial pathogen demonstrates intense inflammatory infiltration. The most impressive inflammatory infiltration is observed during the peak of tick feeding and after spontaneous detachment. Moreover, intradermal needle inoculation of bacteria did not induce extensive skin inflammation nor severe disease outcome. Like with other rickettsial infections, we identified a persistence of ehrlichial antigen at the skin of infected animals. These findings demonstrate induction of an inflammatory response, potentially associated with successful bacterial replication and disease pathogenesis. Our goal is to better understand this complex vector-host-pathogen interaction at the cutaneous interface and its influence in immunopathogenesis of disease severity.