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BALDON, E. J. Mycobacterium leprae Hsp65 influences over the aging process and immunological response of aged genetically selected mice. 2013. 139 p. Ph. D. thesis (Immunology) – Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, 2014. The heat shock proteins (Hsp), conserved molecules among the evolutionary scale, have been used for the development of autoimmunities and tumors treatments. However, the mechanism of action of these proteins in chronic-degenerative processes has not been fully enlightened, since they may be involved in worsening of autoimmune and inflammation, also interfering in immunosenescence. Previous data showed that 9-mo female HIII mice showed reduced survival after M. leprae Hsp65 intraperitoneal administration, which did not occur in aged males HIII or female LIII mice. In order to understand the interference of Hsp65 in the immune system during the aging process, we performed a phenotypic analysis of leukocytes from spleen and blood of aged HIII females after administration of 2.5μg/animal of Hsp65. Additionally, using hybrid mice originated of reciprocal crosses from Selection III strains, namely F1H [♀HIII x ♂LIII] and F1L [♀LIII x ♂HIII], we investigated the genetic influence in Hsp65 susceptibility through analysis of the mean survival time, anti-Hsp65 antibody production and cellular changes in these mice. In the spleen, aged ♀HIII showed increased expression of CD45RA and CD154 in CD4 T lymphocytes, reduction of CD44 in CD8 T lymphocytes and augmented frequency of B cells. In the blood, the administration of Hsp65 in aged ♀HIII resulted in amplified occurrence of CD11c and expression of CD11c and CD11b in granulocytes, whereas the expression of CD80, CD86, CD14 and TLR4 did not change. The survival of aged ♀F1H injected with Hsp65 was reduced compared to the control group, with similar environmental variance and the time between the deaths related to data previously obtained in ♀HIII. ♀F1H, ♂F1H e ♂F1L showed no changes in survival; the antiHsp65 IgG production increased in ♂F1 male mice injected with the protein, and the antiHsp65 IgM was increased after injection regardless of gender. In contrast, ♀F1H and ♀F1L mice showed increased percentage of CD4 + CD45RA + , CD4 + CD154 + , CD8 + , CD8 + CD44 + and CD11c + cells, with augmented expression of CD154, CD44 and CD86; male mice did not present any significant changes in cellularity. We concluded that the inoculation of M. leprae Hsp65 induces in vivo, activation of the immune system, especially in aged HIII and F1 female mice, indicating the physiological actions of the molecule and its ability to modulate immunological characteristics. The susceptibility to the protein can be given by the interaction between specific gender effects in females and some genetic influence of the HIII strain.

Influência da Hsp65 de Mycobacterium leprae sobre o processo de envelhecimento e resposta imune de camundongos geneticamente selecionados.