title: Characterization of Proinflammatory Responses and Innate Signaling Activation in Macrophages Infected with Mycobacterium scrofulaceum.
abstract: Mycobacterium scrofulaceum is an environmental and slow-growing atypical mycobacterium. Emerging evidence suggests that M. scrofulaceum infection is associated with cervical lymphadenitis in children and pulmonary or systemic infections in immunocompromised adults. However, the nature of host innate immune responses to M. scrofulaceum remains unclear. In this study, we examined the innate immune responses in murine bone marrow-derived macrophages (BMDMs) infected with different M. scrofulaceum strains including ATCC type strains and two clinically isolated strains (rough and smooth types). All three strains resulted in the production of proinflammatory cytokines in BMDMs mediated through toll-like receptor-2 and the adaptor MyD88. Activation of MAPKs (extracellular signal-regulated kinase 1/2, and p38, and c-Jun N-terminal kinase) and nuclear receptor (NF)-κB together with intracellular reactive oxygen species generation were required for the expression of proinflammatory cytokines in BMDMs. In addition, the rough morphotypes of M. scrofulaceum clinical strains induced higher levels of proinflammatory cytokines, MAPK and NF-κB activation, and ROS production than other strains. When mice were infected with different M. scrofulaceum strains, those infected with the rough strain showed the greatest hepatosplenomegaly, granulomatous lesions, and immune cell infiltration in the lungs. Notably, the bacterial load was higher in mice infected with rough colonies than in mice infected with ATCC or smooth strains. Collectively, these data indicate that rough M. scrofulaceum induces higher inflammatory responses and virulence than ATCC or smooth strains.
authors.affiliation: Center of Inflammation, Infection & Immunity, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
authors.forename: Ki-Hye
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Chungnam National University School of Medicine, Daejeon 301-747, Korea. ; Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, Korea.
authors.forename: Tae-Sung
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Chungnam National University School of Medicine, Daejeon 301-747, Korea. ; Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, Korea.
authors.forename: Joy G
authors.initials: JG
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Chungnam National University School of Medicine, Daejeon 301-747, Korea. ; Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, Korea.
authors.forename: Jeong-Kyu
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Microbiology, Chungnam National University School of Medicine, Daejeon 301-747, Korea. ; Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, Korea.
authors.forename: Miso
authors.initials: M
authors.lastname: Yang
authors.affiliation: Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, Korea. ; Department of Pathology, Chungnam National University School of Medicine, Daejeon 301-747, Korea.
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Chungnam National University School of Medicine, Daejeon 301-747, Korea. ; Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, Korea.
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
authors.affiliation: Department of Infection Biology, Chungnam National University School of Medicine, Daejeon 301-747, Korea. ; Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, Korea.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Yuk
keywords: MAPKs; MyD88; Mycobacterium scrofulaceum; Nuclear receptor-κB; Proinflammatory cytokines; TLR