Influência da infecção pelo HIV-1 no eixo de sinalização FPRs/AnxA1 e impactos na progressão da doença

• Ano de defesa: 2017
• Autor(a) principal: Rodrigues, Cláudia Mendonça
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Uberlândia; Brasil; Programa de Pós-graduação em Imunologia e Parasitologia Aplicadas
• Palavras-chave em Português: Imunologia; AIDS (Doença); HIV (Vírus); Infecções por HIV; Imunoativação; FPRs; AnxA1; Inflamação; Immunoactivation; Inflammation; CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA
• Link de acesso: https://repositorio.ufu.br/handle/123456789/18954; http://dx.doi.org/10.14393/ufu.te.2017.40

During HIV-1 infection, a systemic immunoactivation triggered by several factors has been a major cause of CD4+ T cell depletion and consequent progression to AIDS. HIV-1 is able to use formylated peptide receptors (FPRs) as co-receptors not usual for infection. FPRs are important regulators of immune response and are key elements in many inflammatory conditions, but have been marginally investigated in HIV-1 infection. Among its ligands, Annexin A1 (AnxA1) has demonstrated a significant anti-inflammatory role in certain pathological conditions, but contradictory function in the peripheral blood. Through the characterization of the gene and protein expression of FPR1, FPR2/ALX, FPR3 and AnxA1 in peripheral blood leukocytes, quantification of AnxA1 in plasma samples and stimulation with functional peptide of AnxA1 (Ac2-26) of peripheral blood mononuclear cells (PBMCs) from HIV-1 positive patients with detectable viral load ( DVL), non-detectable ( NDVL) and healthy donors (control), we investigated the systemic effects of HIV-1 on the expression and function of FPRs, as well as on plasma levels of AnxA1 and its translocation. The aim of this study was to evaluate the relationship between HIV-1 infection and the FPRs/AnxA1 signaling axis and the consequences for the course of the disease. HIV-1 was able to modulate the levels of transcription and protein expression of FPRs in a cell-specific manner with upregulation of FPR3 and downregulation of FPR2. Translocation of AnxA1 was also affected in all cell populations. AnxA1 was significantly detected in plasma samples from patients of CVD group, which may act as an important prognostic marker of patients regarding the efficacy of the treatment. Stimulation of PBMCs with Ac2-26 induced a strong inflammatory response in HIV-1 infected groups, which was partially blocked by their BOC-2 antagonist, suggesting their action via FPR1. This was the first study about the effects of HIV-1 infection on FPRs and how the viral load affects its modulation and the AnxA1 translocation. This suggests a crucial role for the FPRs/AnxA1 signaling axis in immune activation, inflammation and disease progression.