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Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions
Tatiane Costa Quaresma1, Lívia de Aguiar Valentim1, Jorge Rodrigues de Sousa1
1Health Department, Center for Biological and Health Sciences, State University of Para-CCBS, UEPA, Belem 66087-662, Brazil.
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. 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.
Insights
This study reveals distinct macrophage (Mφ) phenotypes in leprosy skin lesions. M1 Mφs dominate tuberculoid and borderline leprosy, while M2 and M4 Mφs are prevalent in Virchowian leprosy, indicating a link between Mφ profiles and disease progression.
Area of Science:
- Immunology
- Dermatology
- Pathology
Background:
- Leprosy, caused by *Mycobacterium leprae*, involves macrophages (Mφs) in its pathogenesis.
- Understanding Mφ subpopulation phenotypes is crucial for elucidating leprosy's inflammatory processes.
Purpose of the Study:
- To investigate the phenotypes of M1, M2, and M4 macrophage subpopulations in leprosy skin lesions.
- To correlate these Mφ phenotypes with different clinical forms of leprosy.
Main Methods:
- Immunohistochemical analysis of skin lesions from treatment-naïve leprosy patients.
- Monolabeling and double-labeling protocols were used to identify M1, M2, and M4 Mφs using specific markers.
- Statistical analysis was performed to compare Mφ phenotypes across Virchowian (VV), Borderline, and Tuberculoid (TT) clinical forms.
Main Results:
- Statistically significant differences in M1, M2, and M4 Mφ phenotypes were observed across VV, Borderline, and TT leprosy forms.
- M1 Mφs were predominant in TT and Borderline leprosy.
- M2 and M4 Mφs were predominant in VV leprosy, with significant correlations noted between certain Mφ phenotypes and clinical forms.
Conclusions:
- Macrophage profiles are closely associated with the chronic inflammatory response in different clinical forms of leprosy.
- The distribution of M1, M2, and M4 Mφ subpopulations varies significantly depending on the leprosy classification.
- These findings highlight the role of specific macrophage phenotypes in leprosy pathogenesis and progression.
