Lucinda Furci1, Elisa Schena2, Paolo Miotto2, Daniela M Cirillo2. 1. Division of Immunity, Transplantation and Infectious Diseases, Emerging Bacterial Pathogens Unit, San Raffaele Scientific Institute, Via Olgettina, 58 20132 Milan, Italy. Electronic address: lucinda.furci@hsr.it. 2. Division of Immunity, Transplantation and Infectious Diseases, Emerging Bacterial Pathogens Unit, San Raffaele Scientific Institute, Via Olgettina, 58 20132 Milan, Italy.
Abstract
BACKGROUND: Mycobacterium tuberculosis (Mtb) has evolved multiple mechanisms to manipulate its cellular niche for its own advantage. Many efforts have been made to understand basal mechanisms of mycobacterial infections. However, the underlying molecular regulation is not fully understood. Recently, a new class of non-coding, small RNAs, called microRNAs (miRNAs), has emerged as important regulators in biological processes, and their involvement in mycobacterial infection has been identified, thus opening a new field of research. METHODS: This study aimed to determine by TaqMan Low Density Array the host genome-wide miRNA expression profile of primary human monocyte-derived macrophages (MDM) infected with two members of the Mtb complex: virulent Mtb H37Rv and the non-virulent vaccine strain Mycobacterium bovis Bacillus Calmette-Guerin (BCG) in comparison with chemically-inactivated Mtb bacilli. RESULTS: The findings of this study showed that infection of MDM with H37Rv or BCG results in a signature of miRNA expression mostly overlapping between the two mycobacteria. A substantially different signature emerged from infection with killed virulent bacilli, suggesting an active influence of live intracellular bacteria on cellular miRNA metabolism. Specifically, Mtb induced miRNA signature is composed of miRNAs well established in immune regulation, miR-155 and miR-146a, as well as a set of miRNAs newly associated with Mtb infection: miR-145, miR-222(∗), miR-27a and miR-27b. All of these miRNAs are predicted to target important immune-related genes. CONCLUSIONS: This study signifies the miRNA host response upon intracellular mycobacterial infection in macrophages, providing new aspects of regulation in host-pathogen interactions, at post-transcriptional levels.
BACKGROUND:Mycobacterium tuberculosis (Mtb) has evolved multiple mechanisms to manipulate its cellular niche for its own advantage. Many efforts have been made to understand basal mechanisms of mycobacterial infections. However, the underlying molecular regulation is not fully understood. Recently, a new class of non-coding, small RNAs, called microRNAs (miRNAs), has emerged as important regulators in biological processes, and their involvement in mycobacterial infection has been identified, thus opening a new field of research. METHODS: This study aimed to determine by TaqMan Low Density Array the host genome-wide miRNA expression profile of primary human monocyte-derived macrophages (MDM) infected with two members of the Mtb complex: virulent MtbH37Rv and the non-virulent vaccine strain Mycobacterium bovisBacillus Calmette-Guerin (BCG) in comparison with chemically-inactivated Mtb bacilli. RESULTS: The findings of this study showed that infection of MDM with H37Rv or BCG results in a signature of miRNA expression mostly overlapping between the two mycobacteria. A substantially different signature emerged from infection with killed virulent bacilli, suggesting an active influence of live intracellular bacteria on cellular miRNA metabolism. Specifically, Mtb induced miRNA signature is composed of miRNAs well established in immune regulation, miR-155 and miR-146a, as well as a set of miRNAs newly associated with Mtb infection: miR-145, miR-222(∗), miR-27a and miR-27b. All of these miRNAs are predicted to target important immune-related genes. CONCLUSIONS: This study signifies the miRNA host response upon intracellular mycobacterial infection in macrophages, providing new aspects of regulation in host-pathogen interactions, at post-transcriptional levels.
Authors: Lin Zheng; Eric Leung; Nelson Lee; Grace Lui; Ka-Fai To; Raphael C Y Chan; Margaret Ip Journal: PLoS One Date: 2015-06-08 Impact factor: 3.240
Authors: Lawrence Shih-Hsin Wu; Shih-Wei Lee; Kai-Yao Huang; Tzong-Yi Lee; Paul Wei-Che Hsu; Julia Tzu-Ya Weng Journal: Biomed Res Int Date: 2014-09-04 Impact factor: 3.411