Elucidation of innate immune response dysfunction of HIV patients: the underlying mechanisms amongst immunological and epigenetic modifications

• Grant number: 11/12199-0
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: June 01, 2012
• End date: September 30, 2016
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Fabiani Gai Frantz
• Grantee: Fabiani Gai Frantz
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Carlos Arterio Sorgi ; Celio Lopes Silva ; Lúcia Helena Faccioli ; Rogério Silva Rosada ; Simone Kashima Haddad
• Associated research grant(s): 18/15066-0 - Epigenetic programming during chronic infectious diseases: tiring out and training the innate immune system, AP.JP2
• Associated scholarship(s): 12/02799-3 - Functional changes of macrophages activated in M1 and M2 patterns derived from HIV-1+ patients in response to fungal and bacterial stimuli, BP.MS

Abstract

Basic researches can help to solve clinical problems, providing tools to transfer results from the bench to the bedside. In developing countries including Brazil, the HIV-1 infection is a major cause of death attributed to infectious diseases, especially when associated with opportunistic co-infections, such as tuberculosis, which affects one third of patients infected with HIV. Multiple studies have shown that macrophages derived from HIV-infected patients exhibit changes in phenotype, problems in their differentiation and functional deficiencies that result in increased susceptibility to opportunistic infections. Among which, include changes in intracellular signaling, which results in altered production of specific cytokines, defects in phagocytosis and killing activity. However, little is known about the mechanisms that cause these defects in macrophages and whether or not epigenetic changes in immune system genes are involved in the dysfunction of macrophages. Thus, the objectives of this project are based on three fronts of investigation, through macrophages derived from HIV+ patients. We will study whether epigenetic changes induced in infection with HIV and HIV/tuberculosis co-infection are related to the regulation of macrophages innate immune response. In parallel, we will investigate how the classical and alternative activation of macrophages are involved in the pathways of inflammatory lipid mediator production after stimulation with bacterial and fungal PAMPs. This study will provide data for evaluation of aspects related to the pathogenesis and alternative therapies for opportunistic infections in AIDS. Finally, biomarkers will be searched for the innate immune response to the introduction of a new clinical parameter in determining the initiation of antiretroviral therapy (ART), since the parameter available in the clinic for initiation of therapy is the count of CD4+ T cells. Together, the overall data of this work can be important in prophylactic approaches, therapies and also for clinical diagnosis. (AU)

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ESPINDOLA, MILENA S.; LIMA, LEONARDO J. G.; SOARES, LUANA S.; CACEMIRO, MAIRA C.; ZAMBUZI, FABIANA A.; GOMES, MATHEUS DE SOUZA; AMARAL, LAURENCE R.; BOLLELA, VALDES R.; MARTINS-FILHO, OLINDO A.; FRANTZ, FABIANI G.. Dysregulated Immune Activation in Second-Line HAART HIV plus Patients Is Similar to That of Untreated Patients. PLoS One, v. 10, n. 12, DEC 18 2015. (11/24026-3, 11/12199-0, 12/02799-3, 11/12512-0)

GALVAO-LIMA, LEONARDO J.; ZAMBUZI, FABIANA A.; SOARES, LUANA S.; FONTANARI, CAROLINE; MEIRELE, ALINE F. GALVA; BRAUER, VERONICA S.; FACCIOLI, LUCIA H.; GAMA, LUCIO; FIGUEIREDO, LUIZ T. M.; BOU-HABIB, DUMITH CHEQUER; et al. HIV-1 Gag and Vpr impair the inflammasome activation and contribute to the establishment of chronic infection in human primary macrophages. Molecular Immunology, v. 148, p. 13-pg., 2022-08-01. (18/15066-0, 11/12199-0)

BRAUER, VERONICA SOARES; ZAMBUZI, FABIANA ALBANI; ESPINDOLA, MILENA SOBRAL; CAVALCANTI NETO, MARINALDO PACIFICO; BORGES PRADO, MORGANA KELLY; CARDOSO, PRISCILLA MARIANE; SOARES, LUANA SILVA; GALVAO-LIMA, LEONARDO JUDSON; LEOPOLDINO, ANDREIA MACHADO; DE BARROS CARDOSO, CRISTINA RIBEIRO; et al. The influence of dehydroepiandrosterone on effector functions of neutrophils. Brazilian Journal of Pharmaceutical Sciences, v. 57, 2021. (11/12199-0)

SOARES, LUANA SILVA; ESPINDOLA, MILENA SOBRAL; ZAMBUZI, FABIANA ALBANI; GALVAO-LIMA, LEONARDO JUDSON; CACEMIRO, MAIRA COSTA; SOARES, MURILO RACY; SANTANA, BARBARA A.; CALADO, RODRIGO T.; BOLLELA, VALDES ROBERTO; FRANTZ, FABIANI GAI. Immunosenescence in chronic HIV infected patients impairs essential functions of their natural killer cells. International Immunopharmacology, v. 84, JUL 2020. (11/24026-3, 18/15066-0, 11/12199-0)

ESPINDOLA, MILENA S.; SOARES, LUANA S.; GALVAO-LIMA, LEONARDO J.; ZAMBUZI, FABIANA A.; CACEMIRO, MAIRA C.; BRAUER, VERNICA S.; FRANTZ, FABIANI G.. HIV infection: focus on the innate immune cells. IMMUNOLOGIC RESEARCH, v. 64, n. 5-6, p. 1118-1132, DEC 2016. (11/24026-3, 11/12199-0, 12/02799-3, 11/12512-0)

ZAMBUZI, FABIANA A.; CARDOSO-SILVA, PRISCILLA M.; ESPINDOLA, MILENA S.; SOARES, LUANA S.; GALVAO-LIMA, LEONARDO J.; BRAUER, VERONICA S.; GOMES, MATHEUS S.; AMARAL, LAURENCE R.; SCHALLER, MATTHEW; BOLLELA, VALDES R.; et al. Identification of promising plasma immune biomarkers to differentiate active pulmonary tuberculosis. CYTOKINE, v. 88, p. 99-107, DEC 2016. (11/12199-0)

LEONARDO J. GALVÃO-LIMA; MILENA S. ESPÍNDOLA; LUANA S. SOARES; FABIANA A. ZAMBUZI; MAIRA CACEMIRO; CAROLINE FONTANARI; VALDES R. BOLLELA; FABIANI G. FRANTZ. Classical and alternative macrophages have impaired function during acute and chronic HIV-1 infection. Brazilian Journal of Infectious Diseases, v. 21, n. 1, p. 42-50, 2017-02-00. (12/02799-3, 11/12199-0)

ESPINDOLA, MILENA S.; SOARES, LUANA S.; GALVAO-LIMA, LEONARDO J.; ZAMBUZI, FABIANA A.; CACEMIRO, MAIRA C.; BRAUER, VERONICA S.; MARZOCCHI-MACHADO, CLENI M.; GOMES, MATHEUS DE SOUZA; AMARAL, LAURENCE R.; MARTINS-FILHO, OLINDO A.; et al. Epigenetic alterations are associated with monocyte immune dysfunctions in HIV-1 infection. SCIENTIFIC REPORTS, v. 8, APR 3 2018. (11/12512-0, 11/12199-0, 17/05365-8)