ArticlePLoS neglected tropical diseases2014
Strong type 1, but impaired type 2, immune responses contribute to Orientia tsutsugamushi-induced pathology in mice.
Article in PLoS neglected tropical diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 64 citations in OpenAlex.
- Single-cell profiling of peripheral blood reveals acute-phase immune dysregulation in human scrub typhus.iMeta · 2026Article
- Longitudinal immune cell dynamics and heterogeneous trajectories in children with scrub typhus: a descriptive pilot study.BMC pediatrics · 2026Article
- Article
- A humanized IFN-γ mouse model reveals skin eschar formation, enhanced susceptibility and scrub typhus pathogenesis.PLoS pathogens · 2026Article
- Longitudinal peripheral blood immune profiling reveals dynamic changes of five major immune cell lineages and their clinical associations in pediatric scrub typhus.Frontiers in immunology · 2026Article
- Differential spleen immune signatures and germinal center responses during acute infection withFrontiers in immunology · 2026Article
- Orientia tsutsugamushi modulates p53, the cell cycle, and genotoxicity to maintain its intracellular niche.Nature communications · 2025Article
- Orientia tsutsugamushi Ank5 promotes NLRC5 cytoplasmic retention and degradation to inhibit MHC class I expression.Nature communications · 2024Article
- Lack of the IFN-γ signal leads to lethal Orientia tsutsugamushi infection in mice with skin eschar lesions.PLoS pathogens · 2024Article
- Human umbilical cord-derived mesenchymal stromal cells improve myocardial fibrosis and restore miRNA-133a expression in diabetic cardiomyopathy.Stem cell research & therapy · 2024Article
- Differential cellular immune responses against Orientia tsutsugamushi Karp and Gilliam strains following acute infection in mice.PLoS neglected tropical diseases · 2023Article
- Alterations in germinal center formation and B cell activation during severe Orientia tsutsugamushi infection in mice.PLoS neglected tropical diseases · 2023Article
- A whole blood intracellular cytokine assay optimised for field site studies demonstrates polyfunctionality of CD4+ T cells in acute scrub typhus.PLoS neglected tropical diseases · 2023Article
- Brain transcriptomics reveal the activation of neuroinflammation pathways during acuteFrontiers in immunology · 2023Article
- Article
- Host transcriptomic profiling of CD-1 outbred mice with severe clinical outcomes following infection with Orientia tsutsugamushi.PLoS neglected tropical diseases · 2022Article
- Gene expression and involvement of signaling pathways during host-pathogen interplay in3 Biotech · 2022Review
- A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model.PLoS neglected tropical diseases · 2022Article
- CCR7/dendritic cell axis mediates early bacterial dissemination inFrontiers in immunology · 2022Article
- Distinct Role of TNFR1 and TNFR2 in Protective Immunity AgainstFrontiers in immunology · 2022Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Scrub typhus is a neglected, but important, tropical disease, which puts one-third of the world's population at risk. The disease is caused by Orientia tsutsugamushi, an obligately intracellular Gram-negative bacterium. Dysregulation in immune responses is known to contribute to disease pathogenesis; however, the nature and molecular basis of immune alterations are poorly defined. This study made use of a newly developed murine model of severe scrub typhus and focused on innate regulators and vascular growth factors in O. tsutsugamushi-infected liver, lungs and spleen. We found no activation or even reduction in base-line expression for multiple molecules (IL-7, IL-4, IL-13, GATA3, ROR-γt, and CXCL12) at 2, 6 and 10 days post-infection. This selective impairment in type 2-related immune responses correlated with a significant activation of the genes for IL-1β, IL-6, IL-10, TNF-α, IFN-γ, as well as CXCR3- and CXCR1-related chemokines in inflamed tissues. The elevated angiopoietin (Ang)-2 expression and Ang-2/Ang-1 ratios suggested excessive inflammation and the loss of endothelial integrity. These alterations, together with extensive recruitment of myeloperoxidase (MPO)-expressing neutrophils and the influx of CD3+ T cells, contributed to acute tissue damage and animal death. This is the first report of selective alterations in a panel of immune regulators during early O. tsutsugamushi infection in intravenously inoculated C57BL/6 mice. Our findings shed new light on the pathogenic mechanisms associated with severe scrub typhus and suggest potential targets for therapeutic investigation.
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