PMID- 25550697 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20141231 LR - 20200929 IS - 1598-2629 (Print) IS - 2092-6685 (Electronic) IS - 1598-2629 (Linking) VI - 14 IP - 6 DP - 2014 Dec TI - Characterization of Proinflammatory Responses and Innate Signaling Activation in Macrophages Infected with Mycobacterium scrofulaceum. PG - 307-20 LID - 10.4110/in.2014.14.6.307 [doi] AB - 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)-kappaB 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-kappaB 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. FAU - Kim, Ki-Hye AU - Kim KH AD - Center of Inflammation, Infection & Immunity, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. FAU - Kim, Tae-Sung AU - Kim TS AD - 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. FAU - Lee, Joy G AU - Lee JG AD - 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. FAU - Park, Jeong-Kyu AU - Park JK AD - 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. FAU - Yang, Miso AU - Yang M AD - 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. FAU - Kim, Jin-Man AU - Kim JM AD - 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. FAU - Jo, Eun-Kyeong AU - Jo EK AD - 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. FAU - Yuk, Jae-Min AU - Yuk JM AD - 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. LA - eng PT - Journal Article DEP - 20141222 PL - Korea (South) TA - Immune Netw JT - Immune network JID - 101137270 PMC - PMC4275388 OTO - NOTNLM OT - MAPKs OT - MyD88 OT - Mycobacterium scrofulaceum OT - Nuclear receptor-kappaB OT - Proinflammatory cytokines OT - TLR COIS- The authors have no financial conflict of interest. EDAT- 2015/01/01 06:00 MHDA- 2015/01/01 06:01 PMCR- 2014/12/01 CRDT- 2015/01/01 06:00 PHST- 2014/10/03 00:00 [received] PHST- 2014/11/12 00:00 [revised] PHST- 2014/11/20 00:00 [accepted] PHST- 2015/01/01 06:00 [entrez] PHST- 2015/01/01 06:00 [pubmed] PHST- 2015/01/01 06:01 [medline] PHST- 2014/12/01 00:00 [pmc-release] AID - 10.4110/in.2014.14.6.307 [doi] PST - ppublish SO - Immune Netw. 2014 Dec;14(6):307-20. doi: 10.4110/in.2014.14.6.307. Epub 2014 Dec 22.