Characterization of Proinflammatory Responses and Innate Signaling Activation in Macrophages Infected with Mycobacterium scrofulaceum
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Mycobacterium scrofulaceum is an environmental andslow-growing atypical mycobacterium. Emerging evidencesuggests that M. scrofulaceum infection is associated withcervical lymphadenitis in children and pulmonary or systemicinfections in immunocompromised adults. However, the natureof host innate immune responses to M. scrofulaceum remainsunclear. In this study, we examined the innate immuneresponses in murine bone marrow-derived macrophages(BMDMs) infected with different M. scrofulaceum strains includingATCC type strains and two clinically isolated strains(rough and smooth types). All three strains resulted in theproduction of proinflammatory cytokines in BMDMs mediatedthrough toll-like receptor-2 and the adaptor MyD88. Activation of MAPKs (extracellular signal-regulated kinase1/2, and p38, and c-Jun N-terminal kinase) and nuclear receptor(NF)-κB together with intracellular reactive oxygenspecies generation were required for the expression of proinflammatorycytokines in BMDMs. In addition, the rough morphotypesof M. scrofulaceum clinical strains induced higherlevels of proinflammatory cytokines, MAPK and NF-κB activation,and ROS production than other strains. When micewere infected with different M. scrofulaceum strains, thoseinfected with the rough strain showed the greatest hepatosplenomegaly,granulomatous lesions, and immune cell infiltrationin the lungs. Notably, the bacterial load was higherin mice infected with rough colonies than in mice infectedwith ATCC or smooth strains. Collectively, these data indicatethat rough M. scrofulaceum induces higher inflammatoryresponses and virulence than ATCC or smoothstrains
Abstract
Mycobacterium scrofulaceum is an environmental andslow-growing atypical mycobacterium. Emerging evidencesuggests that M. scrofulaceum infection is associated withcervical lymphadenitis in children and pulmonary or systemicinfections in immunocompromised adults. However, the natureof host innate immune responses to M. scrofulaceum remainsunclear. In this study, we examined the innate immuneresponses in murine bone marrow-derived macrophages(BMDMs) infected with different M. scrofulaceum strains includingATCC type strains and two clinically isolated strains(rough and smooth types). All three strains resulted in theproduction of proinflammatory cytokines in BMDMs mediatedthrough toll-like receptor-2 and the adaptor MyD88. Activation of MAPKs (extracellular signal-regulated kinase1/2, and p38, and c-Jun N-terminal kinase) and nuclear receptor(NF)-κB together with intracellular reactive oxygenspecies generation were required for the expression of proinflammatorycytokines in BMDMs. In addition, the rough morphotypesof M. scrofulaceum clinical strains induced higherlevels of proinflammatory cytokines, MAPK and NF-κB activation,and ROS production than other strains. When micewere infected with different M. scrofulaceum strains, thoseinfected with the rough strain showed the greatest hepatosplenomegaly,granulomatous lesions, and immune cell infiltrationin the lungs. Notably, the bacterial load was higherin mice infected with rough colonies than in mice infectedwith ATCC or smooth strains. Collectively, these data indicatethat rough M. scrofulaceum induces higher inflammatoryresponses and virulence than ATCC or smoothstrains
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