title: Mycobacterium abscessus ESX-3 plays an important role in host inflammatory and pathological responses during infection.
abstract: Mycobacterial ESX systems are often related to pathogenesis during infection. However, little is known about the function of ESX systems of Mycobacterium abscessus (Mab). This study focuses on the Mab ESX-3 cluster, which contains major genes such as esxH (Rv0288, low molecular weight protein antigen 7; CFP-7) and esxG (Rv0287, ESAT-6 like protein). An esx-3 (MAB 2224c-2234c)-deletional mutant of Mab (Δesx) was constructed and used to infect murine and human macrophages. We then investigated whether Mab Δesx modulated innate host immune responses in macrophages. Mab Δesx infection resulted in less pathological and inflammatory responses. Additionally, Δesx resulted in significantly decreased activation of inflammatory signaling and cytokine production in macrophages compared to WT. Moreover, recombinant EsxG·EsxH (rEsxGH) proteins encoded by the ESX-3 region showed synergistic enhancement of inflammatory cytokine generation in macrophages infected with Δesx. Taken together, our data suggest that Mab ESX-3 plays an important role in inflammatory and pathological responses during Mab infection.
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Yi Sak
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Molecular and Life Science, Hanyang University, Ansan 426-791, South Korea.
authors.forename: Chul-Su
authors.initials: CS
authors.lastname: Yang
authors.affiliation: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.
authors.forename: Loi T
authors.initials: LT
authors.lastname: Nguyen
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Hyo Sun
authors.initials: HS
authors.lastname: Jin
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Choe
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Soo Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Hye-Mi
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Department of Pathology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Jung
authors.affiliation: Department of Pathology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Molecular Mechanism of Antibiotics, Division of Life Science, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, South Korea. Electronic address: jichanjang@gnu.ac.kr.
authors.forename: Ji-Chan
authors.initials: JC
authors.lastname: Jang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D064368:Healthy Volunteers; D006801:Humans; D007113:Immunity, Innate; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008810:Mice, Inbred C57BL; D005810:Multigene Family; D009161:Mycobacterium / Q000235:genetics / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D037521:Virulence Factors
keywords: ESX-3; Host inflammation; Mycobacterium abscessus