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

Kim, Su Young; Koh, Won Jung; Kim, Yee Hyung; Jeong, Byeong‐Ho; Park, Hye Yun; Jeon, Kyeongman; Kim, Jong Seok; Cho, Sang Nae; Shin, Sung Jae

doi:10.1371/journal.pone.0109941

Cited by 22 publications

(16 citation statements)

References 39 publications

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“…These finding is similar to studies performed in MAC infection (93,95). Interestingly, levels of monokine induced by IFNγ (MIG) and IFNγ induced protein (IP-10) could predict treatment outcome (99). A recent small study on cytokine levels in three CF patients with MABS infection compared to three patients with non-CF PNTM infection and healthy controls showed no difference in TNF and IL-1β levels between CF and non-CF patients, however the non-CF patients showed higher TNF and IL-1β production following LPS stimulation (100).…”

Section: The Immune Response In Pulmonary Ntm Infectionsupporting

confidence: 87%

The Rise of Non-Tuberculosis Mycobacterial Lung Disease

et al. 2020

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Section: The Immune Response In Pulmonary Ntm Infectionsupporting

confidence: 87%

The Rise of Non-Tuberculosis Mycobacterial Lung Disease

et al. 2020

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“…When M. abs-R-infected macrophages were treated with IFN-g, the production of proinflammatory cytokines was slightly increased. Accumulating evidence has suggested that a low Th1 cell response, low levels of Th1associated cytokines such as TNF-a and IFN-g, and a delayed infiltration of innate immune cells such as monocytes and macrophages into the lungs could be associated with host susceptibility to the development of NTM disease [22,45]. In this study, we found that MSCs lead to the increased recruitment of inflammatory cells such as monocytes, CD11b high macrophages, and CD4 1 and CD8 1 T cells to the lungs in mice infected with M. abs-R compared with M. abs-R-infected mice not injected with MSCs.…”

Section: Discussionmentioning

confidence: 99%

A Novel Therapeutic Approach Using Mesenchymal Stem Cells to Protect Against Mycobacterium abscessus

Kim

et al. 2016

Stem Cells

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Recent studies have demonstrated the therapeutic potential of mesenchymal stem cells (MSCs) for the treatment of acute inflammatory injury and bacterial pneumonia, but their therapeutic applications in mycobacterial infections have not been investigated. In this study, we demonstrated the use of MSCs as a novel therapeutic strategy against Mycobacterium abscessus (M. abscessus), which is the most drug-resistant and difficult-to-treat mycobacterial pathogen. The systemic intravenous injection of MSCs not only improved mouse survival but also enhanced bacterial clearance in the lungs and spleen. Additionally, MSCs enhanced IFN-c, TNFa, IL-6, MCP-1, nitric oxide (NO) and PGE 2 production and facilitated CD4high macrophage, and monocyte recruitment in the lungs of M. abscessus-infected mice. To precisely elucidate the functions of MSCs in M. abscessus infection, an in vitro macrophage infection system was used. MSCs caused markedly increased NO production via NF-jB activation in M. abscessus-infected macrophages cultured in the presence of IFN-c. Inhibiting NO or NF-jB signaling using specific inhibitors reduced the antimycobacterial activity of MSCs. Furthermore, the cellular crosstalk between TNF-a released from IFN-c-stimulated M. abscessus-infected macrophages and PGE 2 produced by MSCs was necessary for the mycobacterial-killing activity of the macrophages. Finally, the importance of increased NO production in response to MSC administration was confirmed in the mouse M. abscessus infection model. Our results suggest that MSCs may offer a novel therapeutic strategy for treating this drug-resistant mycobacterial infection by enhancing the bacterial-killing power of macrophages. STEM CELLS 2016;34:1957-1970 SIGNIFICANCE STATEMENTMycobacterium abscessus is resistant to many antibiotics, thus making it difficult to obtain a successful treatment outcome. Here, we demonstrated that the administration of mesenchymal stem cell (MSCs) has significant potential in the treatment of M. abscessus infection. We found that the systemic injection of MSCs improved mouse survival and enhanced bacterial clearance in the lungs. In subsequent in vitro studies, we discovered that MSCs increased NO production in M. abscessus-infected macrophages through NF-jB activation in the presence of IFN-g. We further demonstrated that the cellular crosstalk between TNF-a and PGE 2 was essential for the increased NO production in macrophages.

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“…CD4 + T cells differentiate into numerous T cell subpopulation, such as Th1, Th2, Th17, and regulatory T cells (Tregs), a process regulated by specific transcription factors [8,9]. Although the IFN-γ/IL-12 axis, representative of Th1, is central to disseminated MAC-PD susceptibility [10][11][12][13][14][15][16], its role in patients confined to MAC-PD is unclear. In addition to Th1 cells, Th17 cells also play a role in establishing protective immunity against mycobacterial infections by secreting IL-17 which leads to recruitment and activation of neutrophils.…”

Section: Introductionmentioning

confidence: 99%

Characteristics of Circulating CD4+ T Cell Subsets in Patients with Mycobacterium avium Complex Pulmonary Disease

Han

Shin

et al. 2020

JCM

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Although prevalence of Mycobacterium avium complex pulmonary disease (MAC-PD) is increasing, limited data are available regarding vulnerability to Mycobacterium avium complex (MAC) infections. To understand the pathobiology of interaction between MAC and host-immunity, it is important to understand the characteristics for circulating T cells in terms of the immunological phenotype and functional correlates in MAC-PD. We aimed to characterize immunophenotype, cytokine profile, and immune inhibitory receptors of circulating CD4+ T cells in MAC-PD patients. We enrolled 71 MAC-PD and 20 control individuals. Flow cytometric analysis was performed to determine T cell subsets and immune checkpoint markers. Ex vivo cytokine productions in response to MAC were determined using enzyme-linked immunosorbent assay. The frequencies of CD4+ T cells and CD4+IL-17+ T cells decreased, while CD4+IL-4+ T cells and CD4+CD25+Foxp3+ T cells increased in peripheral blood mononuclear cells (PBMCs) of MAC-PD individuals upon MAC stimulation compared with those cells in healthy donor-PBMCs. Additionally, we found increased PD-1, CTLA-4, and TIM-3-expressing T cells in MAC- PD individuals in response to MAC-stimulation, indicating that suppressed T cell-mediated response is associated with the susceptibility to MAC infection. These results may help to explain impaired T cell-mediated responses and pave the way for better strategies to achieve protective immunity against MAC infection.

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

Cited by 22 publications

References 39 publications

The Rise of Non-Tuberculosis Mycobacterial Lung Disease

The Rise of Non-Tuberculosis Mycobacterial Lung Disease

A Novel Therapeutic Approach Using Mesenchymal Stem Cells to Protect Against Mycobacterium abscessus

Characteristics of Circulating CD4+ T Cell Subsets in Patients with Mycobacterium avium Complex Pulmonary Disease

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