ArticlePLoS neglected tropical diseases2016
An Intradermal Inoculation Mouse Model for Immunological Investigations of Acute Scrub Typhus and Persistent Infection.
Article in PLoS neglected tropical diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 44 citations in OpenAlex.
- Clinical features and risk factors for severe pediatric scrub typhus in Liangshan Prefecture, China: A retrospective cohort study.BMC pediatrics · 2026Article
- A humanized IFN-γ mouse model reveals skin eschar formation, enhanced susceptibility and scrub typhus pathogenesis.PLoS pathogens · 2026Article
- High levels of Interleukin - 13 in patients with scrub typhus correlate with disease severity.Scientific reports · 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
- Article
- Humoral Immune Response toZoonoses (Shannon, Ireland) · 2025Article
- A longitudinal molecular surveillance of genetic heterogeneity ofFrontiers in microbiology · 2025Article
- Orientia tsutsugamushi Ank5 promotes NLRC5 cytoplasmic retention and degradation to inhibit MHC class I expression.Nature communications · 2024Article
- Stomach as the target organ of Rickettsia heilongjiangensis infection in C57BL/6 mice identified by click chemistry.Communications biology · 2024Article
- Lack of the IFN-γ signal leads to lethal Orientia tsutsugamushi infection in mice with skin eschar lesions.PLoS pathogens · 2024Article
- Pathological Responses in Asian House Shrews (Microorganisms · 2024Article
- Differential cellular immune responses against Orientia tsutsugamushi Karp and Gilliam strains following acute infection in mice.PLoS neglected tropical diseases · 2023Article
- Orientia tsutsugamushi: A life between escapes.MicrobiologyOpen · 2023Article
- Alterations in germinal center formation and B cell activation during severe Orientia tsutsugamushi infection in mice.PLoS neglected tropical diseases · 2023Article
- Host transcriptomic profiling of CD-1 outbred mice with severe clinical outcomes following infection with Orientia tsutsugamushi.PLoS neglected tropical diseases · 2022Article
- A Murine Model of Waning Scrub Typhus Cross-Protection between Heterologous Strains ofPathogens (Basel, Switzerland) · 2022Article
- Distinct Role of TNFR1 and TNFR2 in Protective Immunity AgainstFrontiers in immunology · 2022Article
- CCR7/dendritic cell axis mediates early bacterial dissemination inFrontiers in immunology · 2022Article
- Comparison of Lethal and Nonlethal Mouse Models ofTropical medicine and infectious disease · 2021Article
- Orientia tsutsugamushi modulates cellular levels of NF-κB inhibitor p105.PLoS neglected tropical diseases · 2021Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Scrub typhus is a neglected tropical disease, caused by Orientia tsutsugamushi, a Gram-negative bacterium that is transmitted to mammalian hosts during feeding by Leptotrombidium mites and replicates predominantly within endothelial cells. Most studies of scrub typhus in animal models have utilized either intraperitoneal or intravenous inoculation; however, there is limited information on infection by the natural route in murine model skin or its related early host responses. Here, we developed an intradermal (i.d.) inoculation model of scrub typhus and focused on the kinetics of the host responses in the blood and major infected organs. Following ear inoculation with 6 x 104 O. tsutsugamushi, mice developed fever at 11-12 days post-infection (dpi), followed by marked hypothermia and body weight loss at 14-19 dpi. Bacteria in blood and tissues and histopathological changes were detected around 9 dpi and peaked around 14 dpi. Serum cytokine analyses revealed a mixed Th1/Th2 response, with marked elevations of MCP-1/CCL2, MIP-1α/CCL3 and IL-10 at 9 dpi, followed by increased concentrations of pro-inflammatory markers (IL-6, IL-12, IFN-γ, G-CSF, RANTES/CCL5, KC/CCL11, IL-1α/β, IL-2, TNF-α, GM-CSF), as well as modulatory cytokines (IL-9, IL-13). Cytokine levels in lungs had similar elevation patterns, except for a marked reduction of IL-9. The Orientia 47-kDa gene and infectious bacteria were detected in several organs for up to 84 dpi, indicating persistent infection. This is the first comprehensive report of acute scrub typhus and persistent infection in i.d.-inoculated C57BL/6 mice. This is a significant improvement over current murine models for Orientia infection and will permit detailed studies of host immune responses and infection control interventions.
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