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Brain transcriptomics reveal the activation of neuroinflammation pathways during acute Orientia tsutsugamushi infection in C57BL/6 mice

ABSTRACT: We performed RNAseq on total RNA extracted from brains of mice infected with Orientia tsutsugamushi to investigate the transcriptomic signature of this tissue throughout infection.

ORGANISM(S): Mus musculus

PROVIDER: GSE227525 | GEO | 2023/05/04

REPOSITORIES: GEO

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Orientia tsutsugamushi

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Alterations in Germinal Center Formation and B Cell Activation during Severe Orientia tsutsugamushi Infection in Mice [Nanostring]

Project description:We performed NanoString analysis on total RNA extracted from spleens of mice infected with Orientia tsutsugamushi to investigate the transcriptomic signature of these cells throughout infection.

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Alterations in Germinal Center Formation and B Cell Activation during Severe Orientia tsutsugamushi Infection in Mice

Project description:We performed RNAseq on total RNA extracted from splenic B cells isolated from mice infected with Orientia tsutsugamushi to investigate the dynamic transcriptomic signature of these cells throughout infection. We then performed differential expression analysis, meta-analysis, and gene set enrichment anaylsis using data obtained by RNA-seq of mock infected (D0) and O. tsutsugamushi-infected mice (D4 and D8).

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Project description:Orientia tsutsugamushi strain:Karp Genome sequencing

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Orientia tsutsugamushi, the agent of scrub typhus, induces an inflammatory program in human macrophages

Project description:Scrub typhus is a life-threatening disease caused by Orientia tsutsugamushi, a bacterium that mainly infects endothelial cells in vitro and in vivo. Evidence suggests that the interaction of O. tsutsugamushi with myeloid cells may play a pivotal role in O. tsutsugamushi infection. We showed here that O. tsutsugamushi intensively replicated within human monocyte-derived macrophages. Bacterial organisms stimulated the expression of a large panel of genes including type I interferon, interferon-stimulated, inflammatory, apoptosis-related genes and induced an M1-type gene response in macrophages. This transcriptional signature was accompanied by functional consequences such as the release of inflammatory cytokines such as Tumor Necrosis Factor and interleukin-gamma. Live O. tsutsugamushi organisms were necessary for type I interferon response and, to a lesser degree, to inflammatory response. As interferon-gamma is known to elicit M1 polarization, we assessed the effect of interferon-gamma on O. tsutsugamushi fate in macrophages. Exogenous interferon-gamma partly inhibited O. tsutsugamushi replication within macrophages. Our results suggest that the inflammatory response induced by O. tsutsugamushi may account for the local and systemic inflammation observed in scrub typhus and that interferon-gamma may be useful as an adjuvant treatment of patients with scrub typhus.

2013-01-29 | GSE38194 | GEO

Orientia tsutsugamushi, the agent of scrub typhus, induces an inflammatory program in human macrophages

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Orientia tsutsugamushi strain:Karp

Project description:Orientia tsutsugamushi strain:Karp Genome sequencing and assembly

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Orientia tsutsugamushi strain:AFSC7

Project description:Orientia tsutsugamushi strain:AFSC7 Genome sequencing and assembly

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Orientia tsutsugamushi strain:AFSC4

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Brain transcriptomics reveal the activation of neuroinflammation pathways during acute <i>Orientia tsutsugamushi</i> infection in mice.

Project description:Scrub typhus, an acute febrile illness caused by Orientia tsutsugamushi (Ot), is prevalent in endemic areas with one million new cases annually. Clinical observations suggest central nervous system (CNS) involvement in severe scrub typhus cases. Acute encephalitis syndrome (AES) associated with Ot infection is a major public health problem; however, the underlying mechanisms of neurological disorder remain poorly understood. By using a well-established murine model of severe scrub typhus and brain RNA-seq, we studied the brain transcriptome dynamics and identified the activated neuroinflammation pathways. Our data indicated a strong enrichment of several immune signaling and inflammation-related pathways at the onset of disease and prior to host death. The strongest upregulation of expression included genes involved in interferon (IFN) responses, defense response to bacteria, immunoglobulin-mediated immunity, IL-6/JAK-STAT signaling, and TNF signaling via NF-κB. We also found a significant increase in the expression of core genes related to blood-brain barrier (BBB) disruption and dysregulation in severe Ot infection. Brain tissue immunostaining and in vitro infection of microglia revealed microglial activation and proinflammatory cytokine production, suggesting a crucial role of microglia in neuroinflammation during scrub typhus. This study provides new insights into neuroinflammation in scrub typhus, highlighting the impact of excessive IFN responses, microglial activation, and BBB dysregulation on disease pathogenesis.

| S-EPMC10326051 | biostudies-literature

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