Possible role of inflammasome in the immune response against virus HIV-1

• Grant number: 09/53575-5
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2010
• End date: March 31, 2011
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Alberto José da Silva Duarte
• Grantee: Alberto José da Silva Duarte
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

NOD-like receptors (NLRs) comprise a large family of intracellular receptors that play an important role in innate immunity in response to recognition of various "damaged" self and inon-self molecules. Some NLRs members are able to regulate the activation of caspase-1 and the production of the pro-inflammatory cytokine IL-1beta, through the formation of a molecular complex called inflammasome. Recent studies indicate that inflammasomes, and NALP3 inflamasomma in particular, is involved in the recognition of both bacteria and viruses. Furthermore, NLRs and inflammasomes appear to be involved in the activation of dendritic cells (DCs) by vaccine adjuvants. Our project hypothesizes that the NLRs proteins, and in particular inflammasomes, may be involved in the immune response against HIV-1, due to its important role in the recognition of other viruses and ssRNA. The study aims to investigate whether the HIV virus is able to activate the inflammasome and, therefore, an inflammatory response triggered by IL-1beta, at the time of infection. This inflammatory process may be important for directing host immune response against the virus and/or the disease progression. Considering recent works on the role of NALP3 in the maturation/activation of DC it is also likely that, if HIV is able to interact with inflammasome, it also affects specific immunity through the activation of antigen presenting cells. This aspect, besides being an important skill for the pathogenesis of infection, could be of great interest for the development of DC-based vaccine therapy against HIV. (AU)

Scientific publications

(5)

(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)

PONTILLO, ALESSANDRA; OSHIRO, TELMA M.; GIRARDELLI, MARTINA; KAMADA, ANSELMO J.; CROVELLA, SERGIO; DUARTE, ALBERTO J. S.. Polymorphisms in Inflammasome' Genes and Susceptibility to HIV-1 Infection. JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, v. 59, n. 2, p. 121-125, FEB 1 2012. (09/53575-5)

PONTILLO, ALESSANDRA; CARVALHO, MARCIA S.; KAMADA, ANSELMO J.; MOURA, RONALD; SCHINDLER, HAIANA C.; DUARTE, ALBERTO J. S.; CROVELLA, SERGIO. Susceptibility to Mycobacterium tuberculosis Infection in HIV-Positive Patients Is Associated With CARD8 Genetic Variant. JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, v. 63, n. 2, p. 147-151, JUN 1 2013. (09/53575-5)

PONTILLO, ALESSANDRA; SILVA, LAIS T.; OSHIRO, TELMA M.; FINAZZO, CLAUDIA; CROVELLA, SERGIO; DUARTE, ALBERTO J. S.. HIV-1 induces NALP3-inflammasome expression and interleukin-1 beta secretion in dendritic cells from healthy individuals but not from HIV-positive patients. AIDS, v. 26, n. 1, p. 11-18, JAN 2 2012. (09/53575-5)

PONTILLO‚ A.; SILVA‚ L.T.; OSHIRO‚ T.M.; FINAZZO‚ C.; CROVELLA‚ S.; DUARTE‚ A.J.S.. HIV-1 induces NALP3-inflammasome expression and interleukin-1β secretion in dendritic cells from healthy individuals but not from HIV-positive patients. AIDS, v. 26, n. 1, p. 11, 2012. (09/53575-5)

PONTILLO, ALESSANDRA; GIRARDELLI, MARTINA; KAMADA, ANSELMO J.; PANCOTTO, JOAO A. T.; DONADI, EDUARDO A.; CROVELLA, SERGIO; SANDRIN-GARCIA, PAULA. Polimorphisms in Inflammasome Genes Are Involved in the Predisposition to Systemic Lupus Erythematosus. AUTOIMMUNITY, v. 45, n. 4, p. 271-278, JUN 2012. (09/53575-5)