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Cutaneous Immunoprofile of Three Spotted Fever Group Rickettsiosis

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE141235 | GEO | 2019/12/03

REPOSITORIES: GEO

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Project description:Rickettsia conorii, the causative agent of the MSF is transmitted to humans by the bite of infected ticks Rhipicephalus sanguineus. The skin thus constitutes an important barrier for the entry and propagation of R. conorii. Given this, analysis of the survival strategies used by the bacterium within infected skin is critical for our understanding of rickettsiosis. Here, we report the first genome-wide analysis of R. conorii gene expression from infected human skin biopsies. Our data showed that R. conorii exhibit a striking transcript signature that was remarkably conserved across patients, regardless of genotype. The expression profiles obtained using custom Agilent microarrays were validated by quantitative RT-PCR. Within eschars, approximately 15% (n = 211) of the total predicted R. conorii ORFs appeared differentially expressed. These genes are mostly down-regulated and encode proteins essential for bacterial replication. Some of the strategies displayed by rickettsiae to overcome the host defense barriers, thus avoiding killing, were also pointed out. The observed up-regulation of rickettsial genes associated with DNA repair is likely to correspond to a DNA-damaging agent enriched environment generated by the host cells to eradicate the pathogens. Survival of R. conorii within eschars also involves adaptation to osmotic stress, changes in cell surface proteins and up-regulation of some virulence factors. Interestingly, in contrast to down-regulated transcripts, we noticed that up-regulated ones rather exhibit a small nucleotide size, most of them being exclusive for the spotted fever group rickettsiae. On the overall, this work provides some insights on how R. conorii counteracts the host cell attack at the site of inoculation which corresponds to the front line of human host defense against rickettsia diffusion and that resembles to battlefield. 9 R.conorii clinical isolates from eschars co-hybridized with reference strain R.conorii Strain Malish 7

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Cutaneous Immunoprofile of Three Spotted Fever Group Rickettsiosis

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