02942nas a2200313 4500000000100000008004100001260001200042653002400054653002700078653004000105653002200145653002700167653001600194653002500210100001600235700002500251700001600276700002300292700001300315700001500328700001500343700001700358245009500375856006900470300000900539490000700548520205900555022001402614 2023 d bMDPI AG10aInfectious Diseases10aMicrobiology (medical)10aGeneral Immunology and Microbiology10aMolecular Biology10aImmunology and Allergy10amacrophages10aImmunohistochemistry1 aQuaresma TC1 ade Aguiar Valentim L1 ade Sousa JR1 ade Souza Aarão TL1 aFuzii HT1 aDuarte MIS1 ade Souza J1 aQuaresma JAS00aImmunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions uhttps://www.mdpi.com/2076-0817/12/10/1225/pdf?version=1696847026 a1-140 v123 a
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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