The interactions between DC and T lymphocytes are responsible for the type of inflammatory/immune response, by the activation of defensive mechanisms of causing damages due to the chronicization of the infection and/or autoaggressivity. The problems that we would like to face regard the role of immunomodulatory molecules (endogenous mediators and conserved molecular structures associated to microorganisms) in regulation of the ability of various DC populations to promote an immune response that could lead to eradication of the pathogen, chronicitation of the infection or autoaggessive events. This ability depends mainly on the cytokine pattern produced by T lymphocytes induced to differentiate by DC following the contact with pathogenic microorganisms and the stimulation by cytokines released by inflammatory cells and DC themselves. The knowledge of the mechanisms of interaction between DC and T lymphocytes, and the possibility to regulate their functional activity will allow the organization of strategies to enhance the defences against infections and/or to limit the auto-aggressivity by the inflammatory and immune systems. Therefore, we will investigate: (1) the functional response of DC to different immunomodulatory factors in terms of differentiation, maturation, cytokine production, phagocytosis and killing of microorganisms (Mycobacterium, Candida, Aspergillus, attenuated measles virus); (2) the kind of polarization of Th lymphocytes (pro- or anti-inflammatory) mediated by DC and the role of immunomodulatory factors and cellular receptors in this process; (3) the interactions between polarized Th lymphocytes and different DC populations in response to pathogenic microorganisms, and the relevance of soluble mediators and cellular receptos in these interactions; (4) the functional properties of DC and Th lymphocytes from patients affected by infective diseases (tuberculosis, candidiasis and aspergillosis) in active or latent form, to find possible correspondences with the in vitro observations.
The cooperation among the researchers who will perform this proposal, working in the fields of general pathology, immunology, microbiology and infective diseases, will lead to integration of the specific knowledges on the mechanisms of natural and acquired defenses, the biology of microorganisms and the pathogen-mediated diseases, and to properly perform the proposed project.