DEFENSIVE RESPONSE OF SENESCENT CELLS TO STAPHYLOCOCCUS AUREUS INFECTION

COLOMBO, MARÍA ISABEL; ULLOA, ANDREA; ROBLEDO, ESTEBAN; AGUILERA, MILTON O.

San Luis

Congreso; XXVII Reunión Anual de la Sociedad de Biología de Cuyo; 2019

Sociedad de Biología de Cuyo

Senescence is defined as a state where somatic cells lose replicative capacity. This mechanism is triggered by different stimuli such as oxidative stress, telomere shortening, DNA damage and chromatin abnormality.The characteristics of senescent cells include irreversible growth arrest, enlarged morphology, expression of cyclin-dependent kinase inhibitor (CDKI), formation of senescence-associated heterochromatin foci, and senescence-associated secretory phenotype (SASP).These changes attempt to prevent damaged cells from proliferating and generating an expansive damage. However, this mechanism can be counterproductive when activated in cells of the immune system as shown by a decrease in the effectiveness of the immune response against pathogens in older people. However, this mechanism can be counterproductive when activated in cells of the immune system as shown by a decrease in the effectiveness of the immune response against pathogens in older people. What could explain the increase in morbidity and mortality of infectious processes in relation to aging. Our work focuses to understand evaluating the response of senescent cells against S. aureus infection.This pathogen is able to replicate intracellularly and to produce a wide spectrum of pathologies in humans ranging from skin infections to life-threatening invasive conditions. Previous results from our laboratory have demonstrated that autophagy plays an important role in the replicative cycle of S. aureus.In addition, it has been demonstrated that senescence blocks autophagy flux. Due that, we propose to study the role of autophagy in the response of senescent cells against S. aureus infection. Taking advantage of the cellular model where senescence is induced by oxidative stress or transient p21 overexpression (CDKI) we were able to evaluate the autophagy response against S. aureus infection.Thus, we have observed that the activation ofsenescence modifies the intracellular distribution of the endocyted microorganisms as well as the number of bacteria recovered by cell at 4 hours post infection. Furthermore, the use of autophagic inducers, as starvation or rapamycin, did not modify the effect observed under senescence activation on S. aureus replication.