Study of intracellular signaling involved in eicosanoid production which are dependent on the expression of phospholipase C from Mycobacterium tuberculosis

• Grant number: 11/01845-9
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2011
• Effective date (End): July 31, 2014
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Lúcia Helena Faccioli
• Grantee: Patricia Aparecida de Assis
• Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 09/07169-5 - Lipid mediators as regulators of immune response, AP.TEM

Abstract

The resistance mechanisms of Mycobacterium tuberculosis (Mtb) against destruction by the host immune system and its ability to multiply within mononuclear phagocytes still are poorly understood. Among the best known virulence factors of Mtb, phospholipase C (PLC) are pivotal in the process of infection, implying in pathogenicity of the bacillus.In our laboratory demonstrated that a strain of Mtb, which expresses PLC, induces exacerbated inflammation leading to tissue damage at the same time that it appears to inhibit the microbicidal activity of alveolar macrophage, favoring the growth of the bacillus in vivo, unlike the strain deficient of these enzymes. The same study,showed a greater production of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) associated with the presence of PLC. Knowing the ability of LTs and PGs as immune response modulators, the control of production of these mediators may have substantial impact on result of infection.Different groups, including ours, have demonstrating the importance of lipid mediators during Mtb infection. Furthermore, some studies suggest the involvement of bacterial PLCs enzymes in inducing the lipid mediators production by the host cell. However, nothing is known about the relationship between Mtb PLCs and the eicosanoids production. Thus, in this project, using strains capable or not to express PLCs, our goal is to investigate the involvement of these Mtb enzymes in the metabolism of lipid mediators in host cell , by studying some intracellular signaling pathways that participate in this process.Understanding the relationship between PLCs and Mtb eicosanoids is an essential step to elucidate a possible virulence mechanism by which this microorganism display pathogenicity.

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)

ASSIS, PATRICIA A.; ESPINDOLA, MILENA S.; PAULA-SILVA, FRANCISCO W. G.; RIOS, WENDY M.; PEREIRA, PRISCILLA A. T.; LEAO, SYLVIA C.; SILVA, CELIO L.; FACCIOLI, LUCIA H. Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages. BMC Microbiology, v. 14, MAY 19 2014. Web of Science Citations: 14.