Functional changes of macrophages activated in M1 and M2 patterns derived from HIV-1+ patients in response to fungal and bacterial stimuli

• Grant number: 12/02799-3
• Support type: Scholarships in Brazil - Master
• Effective date (Start): October 01, 2012
• Effective date (End): January 31, 2014
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal researcher: Fabiani Gai Frantz
• Grantee: Leonardo Judson Galvão de Lima
• Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 11/12199-0 - Elucidation of innate immune response dysfunction of HIV patients: the underlying mechanisms amongst immunological and epigenetic modifications, AP.JP

Abstract

After 30 years of recognition of the Acquired Immunodeficiency Syndrome (AIDS) as a worldwide epidemic caused by Human Immunodeficiency Virus (HIV), many questions about the action of the virus and its interaction with the cells of our immune system remain unanswered or need be better clarified. In Brazil, HIV infection is a major cause of death attributed to infectious diseases, especially when associated with opportunistic co-infections, such as tuberculosis. The beginning of the syndrome is characterized by an abrupt reduction in the number of CD4+ T cells due to cell lyses caused by viral proliferation during active disease. However, with the destruction of these cells, activation of other stages of the immune response (IR) is impaired, compromising the final performance of the immune system. Recent studies have shown that macrophages derived from peripheral blood of HIV+ patients exhibit phenotypic changes, problems of differentiation and functional deficiencies, contributing to the occurrence of opportunistic infections, responsible for high morbidity and mortality of these patients in the advanced stages of the syndrome. The innate IR against opportunistic microorganisms is dependent on the interaction of cells with certain molecules of pathogens and concomitant presence of cytokines. This interaction is characterized by the binding of cellular receptors, known as Pattern Recognition Receptors (PRR), to molecules expressed by pathogens, called PAMPs (Pathogen Associated Molecular Pattern). In general, macrophages are responsible for performing the protection against infections, being activated by two distinct patterns: Classic (M1) and Alternative (M2), when present the GM-CSF and IFN-³ or IL-4, IL -13 and IL-10, respectively. Moreover, some data have suggested that HIV isolated proteins could be related to M2 differentiation in vitro. In this context of immune response dichotomy, the objective of this study is to relate the activation pathways of macrophages with epigenetic changes in different stages of infection, which may be associated with the pattern of macrophages differentiation and chemotactics molecules, favoring the occurrence of opportunistic infections and other co-morbidities characteristics of AIDS.

Scientific publications

(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)

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, Fev. 2017. Web of Science Citations: 3.

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. Web of Science Citations: 6.

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. Web of Science Citations: 7.