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B lymphocytes deficiency results in altered immune response and increased susceptibility to Mycobacterium leprae in a murine leprosy model

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Azevedo, Michelle de C. S. ; Marques, Heloisa ; Binelli, Larissa S. ; Malange, Mariana S. V. ; Devides, Amanda C. ; Fachin, Luciana R. V. ; Soares, Cleverson T. ; Belone, Andrea de F. F. ; Rosa, Patricia S. ; Garlet, Gustavo P. ; Trombone, Ana Paula F.
Número total de Autores: 11
Tipo de documento: Artigo Científico
Fonte: CYTOKINE; v. 165, p. 11-pg., 2023-03-28.
Resumo

Leprosy is a chronic and infectious disease that primarily affects the skin and peripheral nervous system, pre-senting a wide spectrum of clinical forms with different degrees of severity. The distinct host immune response patters developed in the response to the bacillus Mycobacterium leprae, the leprosy etiologic agent, are associated with the spectral clinical forms and outcome of the disease. In this context, B cells are allegedly involved in the disease immunopathogenesis, usually as antibody-producing cells, but also as potential effector or regulatory elements. In order to determine the regulatory B cells role in experimental leprosy, this study evaluated the outcome of M. leprae infection in B cell deficient mice (BKO) and WT C57Bl/6 control, by means of microbio-logical/bacilloscopic, immunohistochemical and molecular analysis, performed 8 months after M. leprae inoc-ulation. The results demonstrated that infected BKO showed a higher bacilli number when compared with WT animals, demonstrating the importance of these cells in experimental leprosy. The molecular analysis demon-strates that the expression of IL-4, IL-10 and TGF-& beta; was significantly higher in the BKO footpads when compared to WT group. Conversely, there was no difference in IFN-& gamma;, TNF-& alpha; and IL-17 expression levels in BKO and WT groups. IL-17 expression was significantly higher in the lymph nodes of WT group. The immunohistochemical analysis revealed that M1 (CD80+) cells counts were significantly lower in the BKO group, while no significant difference was observed to M2 (CD206+) counts, resulting a skewed M1/M2 balance. These results demonstrated that the absence of B lymphocytes contribute to the persistence and multiplication of M. leprae, probably due to the increased expression of the IL-4, IL-10 and TGF-& beta; cytokines, as well as a decrease in the number of M1 macrophages in the inflammatory site. (AU)

Processo FAPESP: 14/13196-3 - Papel das células B na Hanseníase experimental: avaliação da multiplicação bacilar e análise histopatológica do coxim plantar de camundongos nocautes de células B
Beneficiário:Mariana Silva Vieira Malange
Modalidade de apoio: Bolsas no Brasil - Iniciação Científica