Association of receptors for lipid mediators with PRRs in macrophages and dendritic cells

Abstract

Macrophages and dendritic cells (DCs) present membrane receptors (PRRs) that recognize microbial structures, Toll-like receptor family being the prototypic receptors of this group. Another group of PRRs recognize altered self components such as oxidized lipids and dying cells and among them the CD36 was the most studied. Stimulation of these receptors induces early generation of lipid mediators (prostanoids, leukotrienes and PAF), cytokine and other genes transcription leading to a given cellular response. Our working hypothesis is that autocrine activation of receptors for lipid mediators in association with the engagement of PRRs, modifies macrophages and DCs phenotype, with important consequences in infection, tumor growth and clearance of dying cells. In the present study we will investigate the effect of: a) PAFR/CD36 association in tumor microenvironmental cells; b) PAFR in tumor-associated immunosuppression and tumor response to chemotherapy and irradiation; c) PAFR/TLR4 association in DCs function and immune responses in vivo; PAFR association with several TLRs on macrophages phenotype and functions; c) LTB4/TLR4 association in macrophages and its effect on the inflammation and resistance to infection in diabetes. (AU)