Keynote 2
Exploring the Cutaneous Interface of Tick-Borne Rickettsia: What We Know and What We Don't

We present critical advances in elucidating the cutaneous interface dynamics of tick-borne spotted fever group rickettsiae (SFGR). Utilizing integrated murine models and clinical meta-transcriptomics, we demonstrate that the skin microbiome plays a pivotal role in modulating SFGR transmission. In R. raoultii-infected murine skin, we observed a significant increase in Chlamydia abundance, which was identified as a central network hub. Furthermore, vertical transovarial transmission in ticks correlated with escalating rickettsial loads and distinct microbiome profiles, as evidenced by α-diversity and principal coordinate analysis (PCoA) across developmental stages. Analysis of human tick-bite lesions revealed complex early "infectomes," characterized by the co-detection of tick-associated bacteria (Pseudomonas, Acinetobacter, Corynebacterium, Propionibacterium) and viruses (Jingmen tick virus, Bole tick virus 4, Deer tick mononegavirales-like virus). Immunoprofiling of SFGR-positive patient biopsies demonstrated pathogen-specific immune responses: R. sibirica infection induced more pronounced neutrophil infiltration and distinct type I interferon signatures compared to R. raoultii, despite shared vascular pathology. Key knowledge gaps remain, particularly concerning the role of skin microbiota-derived volatiles in influencing tick vector competence, targeted microbiome manipulation for transmission blockade, and human skin microbial signatures that affect pathogen establishment. These findings underscore the necessity of a "One Health" approach to address these emerging public health threats.