ArticlePLoS pathogens2021
Orientia tsutsugamushi selectively stimulates the C-type lectin receptor Mincle and type 1-skewed proinflammatory immune responses.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Chikungunya virus persists in joint-associated macrophages and promotes chronic disease in mice.Nature microbiology · 2026Article
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- A humanized IFN-γ mouse model reveals skin eschar formation, enhanced susceptibility and scrub typhus pathogenesis.PLoS pathogens · 2026Article
- Temporal regulation of macrophage polarization by abnormally innervated CGRP + Sensory nerves following spinal cord injury.Cellular and molecular life sciences : CMLS · 2026Review
- Targeting CLEC4E in immunosuppressive tumour-associated macrophages via BET inhibition.Clinical and translational medicine · 2025Article
- Mincle as a potential intervention target for the prevention of inflammation and fibrosis (Review).Molecular medicine reports · 2024Review
- Lack of the IFN-γ signal leads to lethal Orientia tsutsugamushi infection in mice with skin eschar lesions.PLoS pathogens · 2024Article
- CagA-positiveFrontiers in microbiology · 2024Article
- Differential cellular immune responses against Orientia tsutsugamushi Karp and Gilliam strains following acute infection in mice.PLoS neglected tropical diseases · 2023Article
- C-Type Lectin Receptors-Triggered Antifungal Immunity May Synergize with and Optimize the Effects of Immunotherapy in Hepatocellular Carcinoma.Journal of inflammation research · 2023Article
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- Host transcriptomic profiling of CD-1 outbred mice with severe clinical outcomes following infection with Orientia tsutsugamushi.PLoS neglected tropical diseases · 2022Article
- Distinct Role of TNFR1 and TNFR2 in Protective Immunity AgainstFrontiers in immunology · 2022Article
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- CCR7/dendritic cell axis mediates early bacterial dissemination inFrontiers in immunology · 2022Article
- Antifungal immunity mediated by C-type lectin receptors may be a novel target in immunotherapy for urothelial bladder cancer.Frontiers in immunology · 2022Article
- Pattern Recognition Receptors in Innate Immunity to Obligate Intracellular Bacteria.Zoonoses (Shannon, Ireland) · 2021Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Orientia tsutsugamushi is an obligately intracellular bacterium and the etiological agent of scrub typhus. The lung is a major target organ of infection, displaying type 1-skewed proinflammatory responses. Lung injury and acute respiratory distress syndrome are common complications of severe scrub typhus; yet, their underlying mechanisms remain unclear. In this study, we investigated whether the C-type lectin receptor (CLR) Mincle contributes to immune recognition and dysregulation. Following lethal infection in mice, we performed pulmonary differential expression analysis with NanoString. Of 671 genes examined, we found 312 significantly expressed genes at the terminal phase of disease. Mincle (Clec4e) was among the top 5 greatest up-regulated genes, accompanied with its signaling partners, type 1-skewing chemokines (Cxcr3, Ccr5, and their ligands), as well as Il27. To validate the role of Mincle in scrub typhus, we exposed murine bone marrow-derived macrophages (MΦ) to live or inactivated O. tsutsugamushi and analyzed a panel of CLRs and proinflammatory markers via qRT-PCR. We found that while heat-killed bacteria stimulated transitory Mincle expression, live bacteria generated a robust response in MΦ, which was validated by indirect immunofluorescence and western blot. Notably, infection had limited impact on other tested CLRs or TLRs. Sustained proinflammatory gene expression in MΦ (Cxcl9, Ccl2, Ccl5, Nos2, Il27) was induced by live, but not inactivated, bacteria; infected Mincle-/- MΦ significantly reduced proinflammatory responses compared with WT cells. Together, this study provides the first evidence for a selective expression of Mincle in sensing O. tsutsugamushi and suggests a potential role of Mincle- and IL-27-related pathways in host responses to severe infection. Additionally, it provides novel insight into innate immune recognition of this poorly studied bacterium.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.