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) seeks to elucidate immune signaling involved in vector transmission of pathogens, focusing on tissue-specific innate host responses induced by ehrlichial and rickettsial diseases. We hypothesize that the initial response at the skin site of tick-pathogen interaction is linked to disease progression and severity. Our in vivo murine model of ehrlichiosis, using natural tick transmission, results in increased bacterial replication, dissemination, and more severe outcomes compared to intradermal needle injection of Ehrlichia (Saito and Walker, 2015). The dermal reaction to tick inoculation shows intense inflammatory infiltration, peaking during tick feeding and after detachment, unlike the minimal inflammation seen with needle inoculation. We also identified the persistence of ehrlichial antigen in the skin, suggesting an inflammatory response tied to bacterial replication and pathogenesis. Our objective is to deepen understanding of vector-host-pathogen interactions at the cutaneous interface and their impact on disease severity. Additionally, our Unit explores the interaction between arthropod vectors and pathogens. Our studies reveal significant behavioral changes in infected ticks that favor pathogen transmission, with pathogen-induced responses observed in nervous tissues before and after attachment. These findings highlight a novel pattern of transmission influenced by tick vector activity. This research will identify potential methods to interfere with transmission and targets for blocking pathogen spread, paving the way for innovative strategies to control vector-borne diseases.