Mycobacterium leprae Hsp65 administration reduces the lifespan of aged high antibody producer mice

Abstract

Background

Aging process may result in immune modifications that lead to disruption of innate and acquired immunity mechanisms that may induce chronic-degenerative events. The heat shock proteins (Hsp), phylogeneticaly conserved among organisms, present as main function the ability of folding and refolding proteins, but they also are associated with chronic-degenerative disorders. Here were evaluated the role of M. leprae native Hsp65 (WT) and its point-mutated (K ⁴⁰⁹A) on survival and anti-DNA and anti-Hsp65 antibody production of aged genetically selected mice for high (H _III) and low (L _III) antibody production; data from 120- and 270-days old mice (named “adult” or “aged”, respectively) were compared.

Results

WT Hsp65 administration induces reduction in the mean survival time of adult and aged female H _III mice, this effect being stronger in aged individuals. Surprisingly, the native protein administration increased the survival of aged female L _III when compared to K ⁴⁰⁹A and control groups. No survival differences were observed in aged male mice after Hsp65 proteins inoculation. We observed increase in IgG1 anti-Hsp65 in WT and K ⁴⁰⁹A aged H _III female mice groups and no marked changes in the anti-DNA (adult and aged H _III) and anti-Hsp65 IgG1 or IgG2a isotypes production in adult H _III female and aged male mice. L _III male mice presented increased anti-DNA and anti-Hsp65 IgG2a isotype production after WT or K ⁴⁰⁹A injection, and L _III female groups showed no alterations.

Conclusions

The results revealed that the WT Hsp65 interferes with survival of aged H _III female mice without involvement of a remarkable IgG1 and IgG2a anti-DNA and anti-Hsp65 antibodies production. The deleterious effects of Hsp65 on survival time in aged H _III female mice could be linked to a gender-effect and are in agreement with those previously reported in lupus-prone mice.