Mycobacterium avium subsp. paratuberculosis MAP1889c Protein Induces Maturation of Dendritic Cells and Drives Th2-Biased Immune Responses

Park, Hye‐Soo; Back, Yong Woo; Son, Young Soo; Kim, Hwa Jung

doi:10.3390/cells9040944

Cited by 4 publications

(6 citation statements)

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“…Purified Rv2145c was not cytotoxic in bone marrow-derived macrophages (BMDMs) up to a concentration of 10 μg/ml ( Figure 1B ). We previously reported that MAP1889c, which is homologous with Rv2145c, stimulates DCs and macrophages to increase surface molecule presentation and secrete cytokines ( 23 ). Therefore, we investigated whether Rv2145c could also induce macrophage activation.…”

Section: Resultsmentioning

confidence: 99%

“…We previously reported that Mycobacterium avium subsp. paratuberculosis MAP1889c, which has homology with Rv2145c, induces DC maturation and Th2 responses and promotes Mycobacterium avium growth and IL-10 production in macrophages ( 23 ). In the present study, Rv2145c induced macrophage activation with elevated IL-10 production ( Figure 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…Numerous papers have demonstrated that mycobacterial proteins induce the activation of macrophages or dendritic cells via the TLR2 or TLR4 pathway. Most PE/PPE proteins interact with the TLR2 molecule, but PE9-PE10 interacts with TLR4 ( 46 ), while other proteins, such as Rv2882 ( 47 ), Rv3463 ( 24 ), Rv2299c ( 48 ), and MAP1889c ( 23 ), interact with TLR4. In this study, Rv2145c induced macrophage activation by interacting with TLR4 ( Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…We previously identified Mycobacterium avium subsp. paratuberculosis MAP1889c, which induces maturation of dendritic cells accompanied by elevated IL-10 production and Th2 responses ( 23 ). To investigate the pathogenic role of the protein in stimulating IL-10 production, we identified Mtb Rv2145c (Wag31) with sequence homology to MAP1889c and tested its direct effect on intracellular Mtb survival.…”

Section: Introductionmentioning

confidence: 99%

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Mycobacterium tuberculosis Rv2145c Promotes Intracellular Survival by STAT3 and IL-10 Receptor Signaling

et al. 2021

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Although Mycobacterium tuberculosis (Mtb) is an intracellular pathogen in phagocytic cells, the factors and mechanisms by which they invade and persist in host cells are still not well understood. Characterization of the bacterial proteins modulating macrophage function is essential for understanding tuberculosis pathogenesis and bacterial virulence. Here we investigated the pathogenic role of the Rv2145c protein in stimulating IL-10 production. We first found that recombinant Rv2145c stimulated bone marrow-derived macrophages (BMDMs) to secrete IL-10, IL-6 and TNF-α but not IL-12p70 and to increase the expression of surface molecules through the MAPK, NF-κB, and TLR4 pathways and enhanced STAT3 activation and the expression of IL-10 receptor in Mtb-infected BMDMs. Rv2145c significantly enhanced intracellular Mtb growth in BMDMs compared with that in untreated cells, which was abrogated by STAT3 inhibition and IL-10 receptor (IL-10R) blockade. Expression of Rv2145c in Mycobacterium smegmatis (M. smegmatis) led to STAT3-dependent IL-10 production and enhancement of intracellular growth in BMDMs. Furthermore, the clearance of Rv2145c-expressing M. smegmatis in the lungs and spleens of mice was delayed, and these effects were abrogated by administration of anti-IL-10R antibodies. Finally, all mice infected with Rv2145c-expressing M. smegmatis died, but those infected with the vector control strain did not. Our data suggest that Rv2145c plays a role in creating a favorable environment for bacterial survival by modulating host signals.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mycobacterium tuberculosis Rv2145c Promotes Intracellular Survival by STAT3 and IL-10 Receptor Signaling

et al. 2021

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“…NOD2 further stimulates the transcription factor NF-KB that regulates pro-inflammatory cytokine expression (168). The TLR1, TLR2, and TLR4 genes also code for PRRs that recognize MAP-associated membrane patterns and initiate the host innate and adaptive immune responses in the infected host (169)(170)(171). Another PRR coded by CLEC7A is expressed on antigen presenting cells (APCs) and is known to recognize MAP and initiate cytokine secretion by phagocytic cells through its synergistic action with TLR2 and TLR4 receptors (169).…”

Section: Genomic Studies Related To Johne's Diseasementioning

confidence: 99%

Johne's Disease in Dairy Cattle: An Immunogenetic Perspective

et al. 2021

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Johne's disease (JD), also known as paratuberculosis, is a severe production-limiting disease with significant economic and welfare implications for the global cattle industry. Caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP), JD manifests as chronic enteritis in infected cattle. In addition to the economic losses and animal welfare issues associated with JD, MAP has attracted public health concerns with potential association with Crohn's disease, a human inflammatory bowel disease. The lack of effective treatment options, such as a vaccine, has hampered JD control resulting in its increasing global prevalence. The disease was first reported in 1895, but in recognition of its growing economic impact, extensive recent research facilitated by a revolution in technological approaches has led to significantly enhanced understanding of the immunological, genetic, and pathogen factors influencing disease pathogenesis. This knowledge has been derived from a variety of diverse models to elucidate host-pathogen interactions including in vivo and in vitro experimental infection models, studies measuring immune parameters in naturally-infected animals, and by studies conducted at the population level to enable the estimation of genetic parameters, and the identification of genetic markers and quantitative trait loci (QTL) putatively associated with susceptibility or resistance to JD. The main objectives of this review are to summarize these recent developments from an immunogenetics perspective and attempt to extract the principal and common findings emerging from this wealth of recent information. Based on these analyses, and in light of emerging technologies such as gene-editing, we conclude by discussing potential future avenues for effectively mitigating JD in cattle.

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Antigen-specific cytokine profiles for pulmonary Mycobacterium avium complex disease stage diagnosis

et al. 2023

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IntroductionControlling pulmonary Mycobacterium avium complex (MAC) disease is difficult because there is no way to know the clinical stage accurately. There have been few attempts to use cell-mediated immunity for diagnosing the stage. The objective of this study was to characterize cytokine profiles of CD4+T and CD19+B cells that recognize various Mycobacterium avium-associated antigens in different clinical stages of MAC.MethodsA total of 47 MAC patients at different stages based on clinical information (14 before-treatment, 16 on-treatment, and 17 after-treatment) and 17 healthy controls were recruited. Peripheral blood mononuclear cells were cultured with specific antigens (MAV0968, 1160, 1276, and 4925), and the cytokine profiles (IFN-γ, TNF-α, IL-2, IL-10, IL-13, and IL-17) of CD4+/CD3+ and CD19+ cells were analyzed by flow cytometry.ResultsThe response of Th1 cytokines such as IFN-γ and TNF-α against various antigens was significantly higher in both the on-treatment and after-treatment groups than in the before-treatment group and control (P < 0.01–0.0001 and P < 0.05–0.0001). An analysis of polyfunctional T cells suggested that the presence of IL-2 is closely related to the stage after the start of treatment (P = 0.0309-P < 0.0001) and is involved in memory function. Non-Th1 cytokines, such as IL-10 and IL-17, showed significantly higher responses in the before-treatment group (P < 0.0001 and P < 0.01–0.0001). These responses were not observed with purified protein derivative (PPD). CD19+B cells showed a response similar to that of CD4+T cells.ConclusionThere is a characteristic cytokine profile at each clinical stage of MAC.

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Mycobacterium avium subsp. paratuberculosis MAP1889c Protein Induces Maturation of Dendritic Cells and Drives Th2-Biased Immune Responses

Abstract: Mycobacterium avium subsp.

Cited by 4 publications

References 48 publications

Mycobacterium tuberculosis Rv2145c Promotes Intracellular Survival by STAT3 and IL-10 Receptor Signaling

Mycobacterium tuberculosis Rv2145c Promotes Intracellular Survival by STAT3 and IL-10 Receptor Signaling

Johne's Disease in Dairy Cattle: An Immunogenetic Perspective

Antigen-specific cytokine profiles for pulmonary Mycobacterium avium complex disease stage diagnosis

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