Bing-Fen Yang1, Fei Zhai1, Hong-Juan An1, Jing Jiang1, Zhi-Hong Cao1, Yan-Hua Liu1, Jin-Wen Su1, Ruo Wang1, Xiao-Xing Cheng2. 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. 2. 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. xcheng79@outlook.com.
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.
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.
Authors: Ayesha J Verrall; Marion Schneider; Bachti Alisjahbana; Lika Apriani; Arjan van Laarhoven; Valerie A C M Koeken; Suszanne van Dorp; Emira Diadani; Fitri Utama; Rachel F Hannaway; Agnes Indrati; Mihai G Netea; Katrina Sharples; Philip C Hill; James E Ussher; Reinout van Crevel Journal: J Infect Dis Date: 2020-03-28 Impact factor: 5.226