Mycobacterium massiliense Induces Inflammatory Responses in Macrophages Through Toll-Like Receptor 2 and c-Jun N-Terminal Kinase

Kim, Tae Sung; Kim, Yi Sak; Yoo, Heekyung; Park, Young Kil; Jo, Eun-Kyeong

doi:10.1007/s10875-013-9978-y

Cited by 20 publications

(22 citation statements)

References 46 publications

(82 reference statements)

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“…Furthermore, we confirmed the HGMN2 knock‐down–mediated enhancement of NFκB activation contributes to the increased production of NO by using NFκB inhibitor. Additionally, Mycobacterium massiliense , belongs to the Mycobacterium.abscessus , has been reported to induce pro‐inflammatory cytokines (TNF‐α, IL‐6 and IL‐1β) dependent on JNK signalling not on ERK1/2 or p38 pathway in BMDMs . In our study, we found that HMGN2 knock‐down enhanced all the three signalling pathways, and we need further experiments to proof whether it was responsible for the HMGN2 regulated M1 markers genes expression.…”

Section: Discussionmentioning

confidence: 60%

“…Since 2005, we were the first to reported that the HMGN2 can functionally as an antimicrobial molecule to against bacteria, 28 In order to investigate the functional relevance of the NTM-induced HMGN2 up-regulation, we firstly analysed the production 42 In our study, we found that HMGN2 knock-down enhanced all the three signalling pathways, and we need further experiments to proof whether it was responsible for the HMGN2 regulated M1 markers genes expression.…”

Section: Discussionmentioning

confidence: 82%

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HMGN2 regulates non‐tuberculous mycobacteria survival via modulation of M1 macrophage polarization

Wang

Chen

Ren

et al. 2019

J Cellular Molecular Medi

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Non‐tuberculous mycobacteria (NTM), also known as an environmental and atypical mycobacteria, can cause the chronic pulmonary infectious diseases. Macrophages have been suggested as the main host cell to initiate the innate immune responses to NTM infection. However, the molecular mechanism to regulate the antimicrobial immune responses to NTM is still largely unknown. Current study showed that the NTM clinical groups, Mycobacterium abscessus and Mycobacterium smegmatis, significantly induced the M1 macrophage polarization with the characteristic production of nitric oxide (NO) and marker gene expression of iNOS, IFNγ, TNF‐α, IL1‐β and IL‐6. Interestingly, a non‐histone nuclear protein, HMGN2 (high‐mobility group N2), was found to be spontaneously induced during NTM‐activated M1 macrophage polarization. Functional studies revealed that HMGN2 deficiency in NTM‐infected macrophage promotes the expression of M1 markers and the production of NO via the enhanced activation of NF‐κB and MAPK signalling. Further studies exhibited that HMGN2 knock‐down also enhanced IFNγ‐induced M1 macrophage polarization. Finally, we observed that silencing HMGN2 affected the survival of NTM in macrophage, which might largely relevant to enhanced macrophage polarization into M1 phenotype under the NTM infection. Collectively, current studies thus suggested a novel function of HMGN2 in regulating the anti‐non‐tuberculous mycobacteria innate immunity of macrophage.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 82%

HMGN2 regulates non‐tuberculous mycobacteria survival via modulation of M1 macrophage polarization

Wang

Chen

Ren

et al. 2019

J Cellular Molecular Medi

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“…M. abscessus induces the secretion of tumor necrosis factor (TNF)-α, IL-6, and IL-12p40 in murine macrophages via Toll-like receptor (TLR)-2 [10] . In addition, M. massiliense induces TNF-α and IL-6 production in murine macrophages [11] . Peripheral blood mononuclear cells (PBMCs) from NTM patients were shown to produce less Th1 cytokines (IFN-γ, IL-12, and TNF-α) compared to healthy controls, suggesting that NTM lung disease might reflect defects in the IL-12/IFN-γ pathway [12] , [13] .…”

Section: Introductionmentioning

confidence: 98%

Importance of Reciprocal Balance of T Cell Immunity in Mycobacterium abscessus Complex Lung Disease

et al. 2014

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BackgroundLittle is known about the nature of the host immune response to Mycobacterium abscessus complex (MABC) infection. The aim of the present study was to investigate whether alterations in serum immunomolecule levels after treating MABC lung disease patients with antibiotics can reflect the disease-associated characteristics.MethodsA total of 22 immunomolecules in 24 MABC lung disease patients before and after antibiotic therapy were quantitatively analyzed using a multiplex bead-based system.ResultsIn general, the pre-treatment levels of T helper type 1 (Th1)-related cytokines, i.e., interferon (IFN)-γ and interleukin (IL)-12, and Th2-related cytokines, i.e., IL-4 and IL-13, were significantly decreased in patients compared with control subjects. In contrast, the pre-treatment levels of Th17-related cytokines, i.e., IL-17 and IL-23, were significantly increased in MABC patients. Interestingly, significantly higher levels of IFN-γ-induced protein (IP)-10 and monokine induced by IFN-γprotein (MIG) were detected in patients with failure of sputum conversion at post-treatment compared to patients with successful sputum conversion.ConclusionReduced Th1 and Th2 responses and enhanced Th17 responses in patients may perpetuate MABC lung disease, and the immunomolecules IP-10 and MIG, induced through IFN-γ, may serve as key markers for indicating the treatment outcome.

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“…Numerous studies have reported that mycobacteria and their antigenic components activate intracellular signaling cascade through innate recognition of TLRs ( 9 , 12 , 16 , 17 , 20 ). To determine the roles of TLR2 in mycobacteria-induced production of proinflammatory cytokines in macrophages, BMDMs from TLR2 wild type (WT) and knockout (KO) mice were stimulated with ATCC, 113S, or 114R strains of M. scrofulaceum in an MOI-dependent manner.…”

Section: Resultsmentioning

confidence: 99%

“…We previously found that mycobacterial infection induced phosphorylation of MAPK such as p38, JNK, and ERK1/2, resulting in production of inflammatory cytokines ( 16 , 20 ). To determine whether M. scrofulaceum -induced inflammatory responses were dependent on MAPK signaling, we monitored MAPK activation in macrophages.…”

Section: Resultsmentioning

confidence: 99%

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

Kim

Lee

et al. 2014

Immune Netw

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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.

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Mycobacterium massiliense Induces Inflammatory Responses in Macrophages Through Toll-Like Receptor 2 and c-Jun N-Terminal Kinase

Cited by 20 publications

References 46 publications

HMGN2 regulates non‐tuberculous mycobacteria survival via modulation of M1 macrophage polarization

HMGN2 regulates non‐tuberculous mycobacteria survival via modulation of M1 macrophage polarization

Importance of Reciprocal Balance of T Cell Immunity in Mycobacterium abscessus Complex Lung Disease

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

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