Immune Checkpoints in Leprosy: Immunotherapy As a Feasible Approach to Control Disease Progression

Autor(es):Mostrar menos -

Lima, Hayana Ramos ^[1] ; Gasparoto, Thais Helena ^[1] ; de Souza Malaspina, Tatiana Salles ^[1] ; Marques, Vinicius Rizzo ^[1] ; Vicente, Marina Jurado ^[1] ; Marcos, Elaine Camarinha ^[2] ; Souza, Fabiana Corvolo ^[2] ; Sales Nogueira, Maria Renata ^[2] ; Barreto, Jaison Antonio ^[2] ; Garlet, Gustavo Pompermaier ^[1] ; da Silva, Joao Santana ^[3] ; Brito-de-Souza, Vania Nieto ^[2] ; Campanelli, Ana Paula ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci, Bauru - Brazil

^[2] Lauro de Souza Lima Inst, Bauru - Brazil

^[3] Univ Sao Paulo, Dept Biochem & Immunol, Sch Med Ribeirao Preto, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 8, DEC 11 2017.
• Citações Web of Science: 1

Resumo

Leprosy remains a health problem in several countries. Current management of patients with leprosy is complex and requires multidrug therapy. Nonetheless, antibiotic treatment is insufficient to prevent nerve disabilities and control Mycobacterium leprae. Successful infectious disease treatment demands an understanding of the host immune response against a pathogen. Immune-based therapy is an effective treatment option for malignancies and infectious diseases. A promising therapeutic approach to improve the clinical outcome of malignancies is the blockade of immune checkpoints. Immune checkpoints refer to a wide range of inhibitory or regulatory pathways that are critical for maintaining self-tolerance and modulating the immune response. Programmed cell-death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4, and lymphocyte-activation gene-3 are the most important immune checkpoint molecules. Several pathogens, including M. leprae, are supposed to utilize these mechanisms to evade the host immune response. Regulatory T cells and expression of co-inhibitory molecules on lymphocytes induce specific T-cell anergy/exhaustion, leading to disseminated and progressive disease. From this perspective, we outline how the co-inhibitory molecules PD-1, PD-L1, and Th1/Th17 versus Th2/Treg cells are balanced, how antigen-presenting cell maturation acts at different levels to inhibit T cells and modulate the development of leprosy, and how new interventions interfere with leprosy development. (AU)

• Processo FAPESP: 10/18142-8 - Análise do envolvimento de células T reguladoras na hanseníase humana
• Beneficiário: Ana Paula Campanelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular