Cutaneous Immunoprofile of Three Spotted Fever Group Rickettsiosis

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. Skin biopsies were assessed for the presence of rickettsial infection by PCR and immunohistochemical (IHC) staining, for transcriptomic profiles by RNA-seq