Human macrophage polarization in the response to Mycobacterium leprae genomic DNA

Marin, Alberto; Huss, Kristopher Van; Corbett, John; Kim, Sangjin; Mohl, Jonathon E.; Hong, Bo Young; Cervantes, Jorge

doi:10.1016/j.crmicr.2020.100015

Cited by 3 publications

(5 citation statements)

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“…Studies have identified that are differentially expressed after M. leprae stimulation, regardless of the Mϕ polarization condition. Additionally, upon M. leprae stimulation, Mϕ polarization upregulates the expression of numerous interferon-stimulated genes [82].…”

Section: Discussionmentioning

confidence: 99%

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Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions

Quaresma,

de Aguiar Valentim,

de Sousa

et al. 2023

Pathogens

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Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-α) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-β, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-α e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 ± 1.3, p < 0.0001), Borderline (1.6 ± 0.4, p < 0.0001), and tuberculoid (TT) (12.5 ± 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 ± 2.3, p < 0.0001), Borderline (1.3 ± 0.2, p < 0.0001), and TT (3.2 ± 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 ± 1.7, p < 0.0001), Borderline (1.2 ± 0.2, p < 0.0001), and TT (2.6 ± 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 × TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy.

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Section: Discussionmentioning

confidence: 99%

“…Activated MϕM1 genes showed marked differential expression of genes involved in IFN type I regulation, Mϕ activation, pathogen DNA recognition, and recruitment of effector cells to the inflammatory site in the presence of M. leprae genomic DNA [82]. Type I IFNs are associated with disseminated and progressive lepromatous lesions [83].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions

Quaresma,

de Aguiar Valentim,

de Sousa

et al. 2023

Pathogens

View full text Add to dashboard Cite

show abstract

“…Studies have identified genes that are differentially expressed after M. leprae stimulation, regardless of the Mφ polarization condition. Additionally, upon M. leprae stimulation, Mφ polarization upregulates expression of numerous interferon-stimulated genes [82].…”

Section: Discussionmentioning

confidence: 99%

“…Activated MφM1 genes showed marked differential expression of genes involved in IFN type I regulation, Mφ activation, pathogen DNA recognition, and recruitment of effector cells to the inflammatory site in the presence of M. leprae genomic DNA [82]. Type I IFNs are associated with disseminated and progressive lepromatous lesions [83].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions

Quaresma¹,

Valentin²,

Sousa³

et al. 2023

Preprint

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Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with Leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. We performed simultaneous multiple immunostaining using monoclonal antibodies specific for inducible nitric oxide synthase (iNOS), IL-6, IL-10, IL-13, TNF-α, TGF-β, FGFb, CD163, CD68, arginase-1, MRP8, and MMP7. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 ± 1.3, p &lt; 0.0001), Borderline (1.6 ± 0.4, p &lt; 0.0001), and tuberculoid (TT) (12.5 ± 1.8, p &lt; 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 ± 2.3, p &lt; 0.0001), Borderline (1.3 ± 0.2, p &lt; 0.0001), and TT (3.2 ± 0.7, p &lt; 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 ± 1.7, p &lt; 0.0001), Borderline (1.2 ± 0.2, p &lt; 0.0001), and TT (2.6 ± 0.7, p &lt; 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2×TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy.

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“…The course entailed development of a research question or project theme, a literature search to identify previous knowledge and theory that provides the context and relevance for the project, the development of a rationale for their project along with specific aims, a plan for the execution, laboratory experimentation for the acquisition and analysis of data, and the development of communication skills in the presentation of their project at a SARP symposium. Sixteen students performed a host-pathogen project which included projects evaluating human cells interaction with microbes, bacterial recognition, antimicrobial action, phagocytosis, and the effect of high glucose in the response to pathogens ( 9 – 11 ). Most projects were carried within a 3.5- to 4-month period, with a few being developed though a year.…”

Section: Methodsmentioning

confidence: 99%

The Impact of Experiential Learning in Host-Pathogen Research on Medical Students’ Interests and Attitudes towards Microbiology and Immunology

Cervantes

Hong

2021

J Microbiol Biol Educ.

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Human macrophage polarization in the response to Mycobacterium leprae genomic DNA

Cited by 3 publications

References 54 publications

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions

The Impact of Experiential Learning in Host-Pathogen Research on Medical Students’ Interests and Attitudes towards Microbiology and Immunology

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