Senescent BALB/c mice are able to develop resistance to Leishmania major infection.
Sindrilaru, Mihaela Anca
LizenzStandard (Fassung vom 03.05.2003)
With advancing age, the immune system of animals and humans undergoes characteristic changes, usually resulting in increased susceptibility to infections and malignancies and deficiency in mounting Th2 immune responses. This PhD thesis addresses the question whether the age-related decline in Th2 responses is dominant enough to reduce the generation of Th2 cells and even to bias Tcell differentiation towards a Th1 pattern providing resistance to diseases that require Th1 immune responses for healing. We investigated this issue on the model of experimental leishmaniasis in mice. In this model, genetically resistant mice (like C57) heal cutaneous lesions and clear the infection with L. major by mounting a Th1 immune response with high levels of IFN-gamma; by contrast, genetically susceptible mice (BALB/c) do not heal and succumb under progressive dissemination of the parasites. Surprisingly, susceptible senescent BALB/c mice developed a milder infection than the young ones and in 60% of the cases even healed ulcerations, similarly to the resistant, C57BL/6 mice. Moreover, some senescent BALB/c mice mounted a L. major-specific Th1 response, with elevated release of IFN-gamma upon infection. By sharp contrast, young BALB/c mice developed a susceptibility-characteristic Th2 response. This observation was further sustained by the finding that macrophages from senescent BALB/c mice spontaneously produce higher levels of IL-12 than macrophages from young mice. IL-12 is the main cytokine responsible for the initiation of a host-protective Th1 immune response. Besides aging, we have identified the infection with Murine Hepatitic Virus as a possible second signal, which might have driven the immune response towards a Th1 pattern in senescent mice raised in conventional conditions. Our results are both remarkable and important, as they show for the first time that BALB/c mice might become resistant to infection with L. major without any treatment.
Erstellung / Fertigstellung
Normierte SchlagwörterImmunreaktion [GND]
Leishmania major [MeSH]