Project description:Spotted Fever Group Rickettsiae (SFGR) can cause mild to fatal illness. The early interaction between the host and rickettsia in skin is largely unknown, and the pathogenesis of severe rickettsiosis remains an important topic. A surveillance of SFGR infection by PCR of blood and skin biopsies followed by sequencing, and immunohistochemical detection was performed on patients with a recent tick bite from 2013–2016. Humoral and cutaneous immune profiles were evaluated for different SFGR cases by serum cytokine and chemokine detection, skin immunohistochemical (IHC) staining, and transcriptome sequencing (RNA-seq). A total of 111 SFGR cases were identified, including 79 Candidatus Rickettsia tarasevichiae (CRT), 22 R. raoultii, 8 R. sibirica, and 2 R. heilongjiangensis. The sensitivity to detect SFGR in skin biopsies (9/24, 37.5 %) was significantly higher than in blood samples (105/2671, 3.9 %) (p<0.05). As early as one day after the tick bite, rickettsia could be detected in the skin. R. sibirica infection was more severe than CRT and R. raoultii. Increased levels of serum IL18, IP10, and MIG, and decreased IL2 in R. sibirica febrile patients were observed compared to CRT febrile infections. RNA-seq and IHC staining could not discriminate SFGR infected and uninfected tick-fed skin lesions. The type I interferon (IFN) response was differently expressed between R. sibirica and R. raoultii infection at the cutaneous interface. Severe rickettsiosis might be inclined to induce an increased type I IFN response on the infected skin but which were complicated by the bite of a tick eliciting immune cell infiltration.
Project description:The host response within the eschar of inoculation during Mediterranean spotted fever (MSF) has been poorly studied. Our objective was to evaluate the host response by comparing transcriptional profiles of eschars to controls using a whole-genome microarray. Hierarchical clustering revealed a signature of eschars consisting of 698 genes. The genes included in this signature were mainly up-regulated and were predominantly associated with immune response and signalling. New molecules involved notably in microbicidal and innate immunity response have also been found up-regulated in eschars such as MMP1, Defensin β4, the proinflammatory S100A9, and the T cell attracting CCL-18. Genes down-regulated were mainly associated with biological regulation. We also observed that eschars from severe cases of MSF displayed a specific signature with notably difference in degree of modulation compared to eschars from non severe MSF cases. Some parameters identified in this work should be tested as biomarkers for prognostic assessment in future studies.