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Mesenchymal-epithelial Transition Factor Regulates Monocyte Function during Mycobacterial Infection via Indoleamine 2,3-dioxygenase

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Abstract

Objective

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), causes an estimated 1.6 million human deaths annually, but the pathogenesis of TB remains unclear. Immunity plays a critical role in the onset and outcome of TB. This study aimed to uncover the roles of innate and adaptive immunity in TB.

Methods

The gene expression profiles generated by RNA sequencing from human peripheral blood mononuclear cells (PBMCs) stimulated with or without Mtb strain H37Rv antigens were analyzed. A total of 973 differentially expressed mRNAs were identified.

Results

The differentially expressed genes were enriched in innate immunity signaling functions. The mesenchymal-epithelial transition factor (MET) gene was significantly upregulated in CD14+ monocytes. A MET inhibitor improved the uptake of the BCG strain by monocytes and macrophages as well as inhibited the expression of indoleamine 2,3-dioxygenase (IDO). The expression of IDO was increased in PBMCs stimulated with Mtb antigens, and the IDO inhibitor promoted the expression of CD40, CD83, and CD86.

Conclusion

Our results might provide clues regarding the immunomodulatory mechanisms used by Mtb to evade the host defense system.

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Authors and Affiliations

  1. Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, the Eighth Medical Center of Chinese PLA General Hospital, Beijing, 100091, China

    Bing-fen Yang, Fei Zhai, Hong-juan An, Jing Jiang, Zhi-hong Cao, Yan-hua Liu, Jin-wen Su, Ruo Wang & Xiao-xing Cheng

Authors
  1. Bing-fen Yang
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  2. Fei Zhai
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  3. Hong-juan An
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  4. Jing Jiang
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  5. Zhi-hong Cao
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  6. Yan-hua Liu
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  7. Jin-wen Su
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  8. Ruo Wang
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  9. Xiao-xing Cheng
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Corresponding author

Correspondence to Xiao-xing Cheng.

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The authors declare no conflicts of interest.

Additional information

This study was supported by the Thirteen-Fifth Mega-Scientific Project on “Prevention and Treatment of AIDS, Viral Hepatitis and Other Infectious Diseases” (No. 2017ZX10201301-007-002), the National Natural Science Foundation of China (No. 81571961 and No. 82072233), and the 309th Hospital (No. 2017ZD-007).

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Yang, Bf., Zhai, F., An, Hj. et al. Mesenchymal-epithelial Transition Factor Regulates Monocyte Function during Mycobacterial Infection via Indoleamine 2,3-dioxygenase. CURR MED SCI 42, 407–416 (2022). https://doi.org/10.1007/s11596-022-2518-3

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  • DOI: https://doi.org/10.1007/s11596-022-2518-3

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