title: Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production.
abstract: Mycobacterium tuberculosis (MTB) is a hard-to-eradicate intracellular microbe, which escapes host immune attack during latent infection. Recent studies reveal that mesenchymal stem cells (MSCs) provide a protective niche for MTB to maintain latency. However, the regulation of mycobacterial residency in MSCs in the infectious microenvironment remains largely unknown. Here, we found that macrophage-mediated inflammatory response during MTB infection facilitated the clearance of bacilli residing in mouse MSCs. Higher inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production were observed in mouse MSCs under macrophage-mediated inflammatory circumstance. Blocking NO production in MSCs increased the survival of intracellular mycobacteria, indicating NO-mediated antimycobacterial activity. Moreover, both nuclear factor κB (NF-κB) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways were involved in iNOS expression and NO production in inflammatory microenvironment. Furthermore, pro-inflammatory cytokine interleukin-1β could trigger NO production in MSCs and exert anti-mycobacterial activity via NF-κB signaling pathway. Neutralization of interleukin-1β in macrophage-mediated inflammatory microenvironment dampened the ability of mouse MSCs to produce NO. Together, our findings demonstrated that macrophage-mediated inflammatory response during mycobacterial infection promotes the clearance of bacilli in mouse MSCs by increasing NO production, which may provide a better understanding of latent MTB infection.
authors.affiliation: Program of Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Institute of Tuberculosis Control, Key laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: Program of Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Institute of Tuberculosis Control, Key laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Traditional Chinese Medicine, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Heping
authors.initials: H
authors.lastname: Xie
authors.affiliation: Program of Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Institute of Tuberculosis Control, Key laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Program of Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Institute of Tuberculosis Control, Key laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Ming
authors.affiliation: Program of Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Institute of Tuberculosis Control, Key laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Li
authors.affiliation: Program of Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Institute of Tuberculosis Control, Key laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Li
authors.affiliation: Program of Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Institute of Tuberculosis Control, Key laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Minhao
authors.initials: M
authors.lastname: Wu
authors.affiliation: Program of Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Sitang
authors.initials: S
authors.lastname: Gong
authors.affiliation: Program of Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Institute of Tuberculosis Control, Key laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D053612:Janus Kinases / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000382:microbiology*; D051379:Mice; D050296:Microbial Viability; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D050791:STAT Transcription Factors; D009569:Nitric Oxide; D053612:Janus Kinases