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Epigenetic programming during chronic infectious diseases: tiring out and training the innate immune system

Abstract

Epigenetic mechanisms are associated with training/programming and polarization of immune cells, which can be induced by the presence of cytokines and molecules present in the microenvironment, like PAMPs (Pathogen-associated molecular pattern) or other mediators of inflammation. Our hypothesis is that during chronic infections such as HIV and TB, PAMPs, cytokines or extracellular vesicles containing epigenetic modifiers, act on non-stimulated cells, causing them to undergo deleterious epigenetic changes that will define the prognosis of diseases. During pulmonary M. tuberculosis infection, cytokines and PAMPs may fall into the circulation and act on circulating or progenitor cells, inducing the training of the innate immune response. On the other hand, in HIV patients, there is a cytokine storm due to disruption of the intestinal barrier and virus immune response. The exacerbated inflammation is associated with the induction of the senescence of innate immune system during infection and uncontrolled inflammatory response. We have shown that monocytes from HIV-infected individuals undergo epigenetic changes that are related to the lack of control in the production of inflammatory cytokines by these cells and in their effector function. In this project, we will test the possibility that extracellular vesicles produced by leukocytes during HIV infection could act in the expansion of the immune senescence phenotype and determine the content of extracellular vesicles present in the plasma of HIV-infected patients. In Tuberculosis, we will evaluate how different conditioning environments can train neutrophils, also determining the epigenetic signature of these profiles and associating the functions and phenotypes of each cell subtype. In addition, we will also evaluate the effects of epidrugs in modulating the function and phenotype of immune cells. (AU)

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Scientific publications (4)
(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)
ZAMBUZI, FABIANA ALBANI; CARDOSO-SILVA, PRISCILLA MARIANE; CASTRO, RICARDO CARDOSO; FONTANARI, CAROLINE; EMERY, FLAVIO DA SILVA; FRANTZ, FABIANI GAI. Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation. CELLS, v. 10, n. 4 APR 2021. Web of Science Citations: 0.
CASTRO, RICARDO CARDOSO; GONCALES, RELBER AGUIAR; ZAMBUZI, FABIANA ALBANI; FRANTZ, FABIANI GAI. Notch signaling pathway in infectious diseases: role in the regulation of immune response. Inflammation Research, v. 70, n. 3 FEB 2021. Web of Science Citations: 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. Web of Science Citations: 0.
LOUREIRO, LUMA DA COSTA; LOUREIRO, LUANA DA COSTA; GABRIEL-JUNIOR, EDSON ALVES; ZAMBUZI, FABIANA ALBANI; FONTANARI, CAROLINE; SALES-CAMPOS, HELIOSWILTON; FRANTZ, FABIANI GAI; FACCIOLI, LUCIA HELENA; SORGI, CARLOS ARTERIO. Pulmonary surfactant phosphatidylcholines induce immunological adaptation of alveolar macrophages. Molecular Immunology, v. 122, p. 163-172, JUN 2020. Web of Science Citations: 1.

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