Research Article: Elimination of Pseudomonas aeruginosa through Efferocytosis upon Binding to Apoptotic Cells

Date Published: December 15, 2016

Publisher: Public Library of Science

Author(s): Darío Capasso, María Victoria Pepe, Jéssica Rossello, Paola Lepanto, Paula Arias, Valentina Salzman, Arlinet Kierbel, Daniel J. Wozniak.

http://doi.org/10.1371/journal.ppat.1006068

Abstract

For opportunistic pathogens such as Pseudomonas aeruginosa, the mucosal barrier represents a formidable challenge. Infections develop only in patients with altered epithelial barriers. Here, we showed that P. aeruginosa interacts with a polarized epithelium, adhering almost exclusively at sites of multi-cellular junctions. In these sites, numerous bacteria attach to an extruded apoptotic cell or apoptotic body. This dead cell tropism is independent of the type of cell death, as P. aeruginosa also binds to necrotic cells. We further showed that P. aeruginosa is internalized through efferocytosis, a process in which surrounding epithelial cells engulf and dispose of extruded apoptotic cells. Intracellularly, along with apoptotic cell debris, P. aeruginosa inhabits an efferocytic phagosome that acquires lysosomal features, and is finally killed. We propose that elimination of P. aeruginosa through efferocytosis is part of a host defense mechanism. Our findings could be relevant for the study of cystic fibrosis, which is characterized by an exacerbated number of apoptotic cells and ineffective efferocytosis.

Partial Text

Pseudomonas aeruginosa is a ubiquitous environmental Gram-negative bacterium and an opportunistic pathogen. It is the causative agent of both acute and chronic human infections. Acute infections are major problems in immunocompromised patients, burn victims and patients requiring mechanical ventilation. Chronic pulmonary infections with P. aeruginosa severely impair the quality of life and life expectancy of cystic fibrosis (CF) patients and are a major factor contributing to their mortality [1, 2]. For opportunistic pathogens such as P. aeruginosa, the mucosal barrier represents a formidable challenge for colonization and bacterial-mediated damage. Thus, infections develop only in patients with altered epithelial cell barriers, including direct trauma, indwelling catheters, or patients receiving cytotoxic chemotherapy. Regarding CF, the sequence of events predisposing to airway infection has been debated for years. A consensus now exists that the respiratory tract pathophysiology in CF largely results from the inability to secrete Cl− and regulate Na+ absorption, which causes dehydration and accumulation of hyper-viscous mucus [3]. CF is also characterized by robust airway inflammation and accumulation of apoptotic cells [4, 5].

In the present study, we showed that P. aeruginosa adheres to apoptotic cells extruded from the epithelial barrier and is then internalized through efferocytosis by surrounding epithelial cells. As mentioned, a polarized epithelium provides a sufficient barrier to prevent P. aeruginosa infection. In healthy individuals, apoptotic cells are quickly removed and disposed of. However, contexts that favor the presence of dead cells might offer an opportunity for P. aeruginosa colonization.

 

Source:

http://doi.org/10.1371/journal.ppat.1006068

 

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