Characterization of Proinflammatory Responses and Innate Signaling Activation in Macrophages Infected withMycobacterium 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.

Chitosan promotes immune responses, ameliorating total mature white blood cell numbers, but increases glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, and ameliorates lactate dehydrogenase levels in leukemia mice in vivo

“…Furthermore, chitosan treatment at both doses significantly decreased WBC numbers compared to acetic acid treatment only. In human immune responses for against invading foreign antigens, T and B cells, monocytes and macrophages serve critical roles, and macrophages are responsible for phagocytosis to destroy antigens ( 30 ), and serve important roles in innate immunity ( 31 , 32 ). Thus, it is well known that agents increase immune responses, and one hallmark is increased macrophage phagocytosis.…”

In vitro antioxidative and anti-inflammatory effects of the compound K-rich fraction BIOGF1K, prepared from Panax ginseng

“…These two major pathways participate in the release of proinflammatory cytokines and inflammatory mediators. Free radicals such as reactive oxygen species (ROS) are highly reactive molecules that are generated in micro- or macrolevel inflammatory responses [16], [17]. Oxidative stress can damage proteins, DNA, and small molecules other than lipids.…”

Pyrrole-Derivative of Chalcone, (E)-3-Phenyl-1-(2-Pyrrolyl)-2-Propenone, Inhibits Inflammatory Responses via Inhibition of Src, Syk, and TAK1 Kinase Activities

“…RAW264.7 or HEK293 cells (5×10 6 cells/ml) were washed three times in cold PBS and lysed in lysis buffer as reported previously (Kim et al ., 2014a). Nuclear lysates were prepared using a three-step procedure (Byeon et al ., 2008).…”