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Updated: Feb 10, 2026

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
Published on: June 9, 2017
Orientia tsutsugamushi binds to multiple C-type lectin receptors
Véronique Hefter1,2, Sabine Mayer-Lambertz3, Zacharias Orfanos1
1Institute of Virology, Philipps University Marburg, Marburg, Germany.
This study identifies C-type lectin receptors (CLRs) that bind Orientia tsutsugamushi, the cause of scrub typhus. Mincle, a CLR, modulates innate immunity by regulating cytokine production during infection.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Orientia tsutsugamushi, the scrub typhus agent, has an unusual cell wall lacking typical pathogen patterns but rich in neutral glycans.
- Phagocyte recognition of O. tsutsugamushi involves a heat-stable ligand, but its identity and sensing receptors are unclear.
- While Toll-like receptors (TLRs) and NOD-like receptors (NLRs) in innate immunity are known, C-type lectin receptors (CLRs) in O. tsutsugamushi recognition are unexplored.
Purpose of the Study:
- To identify C-type lectin receptors (CLRs) involved in Orientia tsutsugamushi recognition.
- To investigate the role of Mincle in the innate immune response to O. tsutsugamushi.
- To elucidate the immunomodulatory functions of CLR-mediated recognition during scrub typhus.
Main Methods:
- Screening of CLR-Fc fusion proteins using flow cytometry to detect O. tsutsugamushi binding.
- Assessing Mincle upregulation and cytokine induction in bone marrow-derived dendritic cells (BMDCs) stimulated with O. tsutsugamushi.
- Analyzing Mincle and Dectin-1 expression in vivo during O. tsutsugamushi infection.
Main Results:
- Orientia tsutsugamushi bound to mouse CLRs (Mincle, Dectin-1, Langerin, DCL-1) and human DC-SIGN.
- Mincle binding was calcium-dependent, suggesting carbohydrate recognition.
- Heat-inactivated O. tsutsugamushi induced Mincle expression in BMDCs via a MyD88-dependent pathway, indicating TLR-CLR crosstalk.
- Mincle deficiency did not affect TNF-α induction but influenced interleukin-27 and CXCL-10 mRNA levels.
- In vivo, Mincle expression increased while Dectin-1 decreased during O. tsutsugamushi infection.
Conclusions:
- Multiple CLRs, including Mincle, Dectin-1, Langerin, DCL-1, and DC-SIGN, act as receptors for Orientia tsutsugamushi.
- Mincle plays a significant role in modulating the innate immune response to O. tsutsugamushi, rather than simply driving pro-inflammatory signals.
- Mincle-mediated immunoregulation is crucial for shaping the inflammatory landscape during scrub typhus infection.
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