Pseudomonas aeruginosa INTERNALIZATION THROUGH EFFEROCYTOSIS UPON BINDING TO APOPTOTIC CELLS: IMMUNE RESPONSE AND BACTERIAL CLEARANCE

MARIA VICTORIA PEPE; ADRIANA JAGER; PAULA ARIAS; DARÍO CAPASSO; LORENA CORIA; JULIANA CASSATARO; ARLINET KIERBEL

Congreso; Reunión Conjunta de Sociedades de Biociencias 2017; 2017

Pseudomonas aeruginosa (PA) is an opportunistic pathogen that infects vulnerable patients, such as those with cystic fibrosis (CF). An advance towards understanding infections caused by PA would be to elucidate the mechanisms that operate in the bacteria-host interplay. We have shown that PA exhibits a remarkable tropism towards dead cells. As bacteria interact with a polarized epithelium, they attach and aggregate almost exclusively on extruded apoptotic cells, while the rest of the surface seems reluctant to bacterial adhesion. We further showed that PA is internalized by epithelial cells surrounding the infected apoptotic cell through efferocytosis, a process in which apopotic cells are engulfed and disposed of by other cells. Bacteria are then eliminated intracellularly. Here we show that two previously characterized PA cystic fibrosis isolates (mucoid/non-mucoid) also showed adhesion to extruded apoptotic cells, internalization of bacteria through efferocytosis and a similar intracellular survival pattern. The small GTPase Rac1 has been shown to be a key regulator of apoptotic cell engulfment. We used a MDCK cell line that expressed a dominant-negative version of Rac1. These cells not only showed impaired uptake of apoptotic cells but also diminished PA internalization. We speculate that bacteria-laden apoptotic cells are targets for professional phagocytes affecting thus both the innate and the adaptive immune responses. We have now extended our analysis to macrophages (J774 macrophage-like) and dendritic cells (from mouse bone marrow). We have seen that professional phagocytes are able to internalize bacteria-laden apoptotic material. We are on our way to evaluate how this affects cytokine´s production, antigen presentation pathway and bacterial killing. Our studies may help to understand why contexts such as CF, which is characterized by chronic lung inflammation, unusual production of apoptotic cells and impaired efferocytosis, favor PA colonization.