Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Tatiane Costa Quaresma
ORCID logo ,
Livia de Aguiar Valentin
ORCID logo ,
Jorge Rodrigues de Sousa
,
Tinara Aarão
,
Hellen Thaís Fuzii
,
Maria Irma Seixas Duarte
ORCID logo ,
Juarez Souza
,
Juarez Antônio Simões Quaresma
*
Version 1 : Received: 24 January 2023 / Approved: 25 January 2023 / Online: 25 January 2023 (10:53:01 CET)

A peer-reviewed article of this Preprint also exists.

Quaresma, T.C.; de Aguiar Valentim, L.; de Sousa, J.R.; de Souza Aarão, T.L.; Fuzii, H.T.; Duarte, M.I.S.; de Souza, J.; Quaresma, J.A.S. Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions. Pathogens 2023, 12, 1225. Quaresma, T.C.; de Aguiar Valentim, L.; de Sousa, J.R.; de Souza Aarão, T.L.; Fuzii, H.T.; Duarte, M.I.S.; de Souza, J.; Quaresma, J.A.S. Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions. Pathogens 2023, 12, 1225.

Abstract

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 < 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.

Keywords

Leprosy; macrophages; immunohistochemistry; immunology

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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