MiR-23a-5p modulates mycobacterial survival and autophagy during mycobacterium tuberculosis infection through TLR2/MyD88/NF-κB pathway by targeting TLR2.
Autophagy plays a pivotal role in activating the antimicrobial host defense against Mycobacterium tuberculosis (M.tb.). The emerging roles of microRNAs (miRNAs) in regulating immune responses have attracted increasing attention in recent years. Appreciating the potential of host-directed therapies designed to control autophagy during mycobacterial infection, we focused on the influence of miR-23a-5p on the activation of macrophage autophagy during M.tb. infection in bone marrow-derived macrophages (BMDMs) and murine RAW264.7 cells. Here, we demonstrated that M.tb.-infection of macrophages lead to markedly enhanced expression of miR-23a-5p in a time- and dose-dependent manner. Furthermore, forced expression of miR-23a-5p accelerated the survival rate of intracellular mycobacteria, while transfection with miR-23a-5p inhibitors attenuated mycobacterial survival. More importantly, overexpression of miR-23a-5p dramatically prevented M.tb.-induced activation of autophagy in macrophages, whereas inhibitors of miR-23a-5p remarkably accelerated M.tb.-induced autophagy. Mechanistically, miR-23a-5p is able to modulate TLR2/MyD88/NF-κB signaling activity by targeting TLR2 in RAW264.7 cells in response to M.tb.-infection. Collectively, these findings demonstrated that miR-23a-5p modulated the innate host defense by promoting mycobacteria survival and inhibiting the activation of autophagy against M.tb. through TLR2/MyD88/NF-κB pathway by targeting TLR2, which may provide a promising therapeutic target for tuberculosis.
Respiratory and Critical Care Medicine, Tangdu Hospital, The Fourth Military Medical University, No. 1 Xinsi Road, Xi'an 710038, Shaanxi, PR China.
Xing
X
Gu
Department of Respiratory Medicine, People's Hospital of BaoJi City, Baoji 721000, Shaanxi, PR China.
Yan
Y
Gao
Respiratory and Critical Care Medicine, Tangdu Hospital, The Fourth Military Medical University, No. 1 Xinsi Road, Xi'an 710038, Shaanxi, PR China. Electronic address: deguang@fmmu.edu.cn.
De-Guang
DG
Mu
Respiratory and Critical Care Medicine, Tangdu Hospital, The Fourth Military Medical University, No. 1 Xinsi Road, Xi'an 710038, Shaanxi, PR China. Electronic address: enqingfu66@163.com.
En-Qing
EQ
Fu
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D001483:Base Sequence; D005786:Gene Expression Regulation; D042541:Intracellular Space / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D050296:Microbial Viability; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D000067996:RAW 264.7 Cells; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D014376:Tuberculosis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology
D020413:3' Untranslated Regions; D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051195:Toll-Like Receptor 2
Autophagy; Mycobacterium tuberculosis (M.tb.); TLR2/MyD88/NF-κB pathway; miR-23a-5p