The Protective Effect of Probiotics on Pseudomonas Aeruginosa Infection by Regulating the Autophagy and Inflammasomes of Intestinal Epithelial Cells and Macrophages

Pseudomonas aeruginosa (P. aeruginosa), carriers the highest case fatality rate of all gram-negative infections. Although rare, P. aeruginosa sepsis is often rapidly progressive, and can occur with a high mortality rate in previously healthy children. Moreover, the emergence of multidrug resistant P. aeruginosa has become a major concern in the hospital setting. Therefore, effective immunotherapy may be a useful alternative therapy administered either alone or in combination with antibiotic chemotherapy. We have demonstrated the innate immunity of intestinal epithelial cells (IECs) to P. aeruginosa infection (BMC Microbiol. 2014;14:275). In additional, the incidence of diarrhoea was reported in half of the included studies in a Cochrane review surveying the reduced incidence of ventilator-associated pneumonia (VAP) by probiotics. Both imply the gut plays a major role on P. aeruginosa infection, and probiotics could act as the protective therapy on P. aeruginosa infection. The autophagy and inflammasome pathways are innate immunity for controlling invading pathogens. Increasing evidence has identified the critical role of autophagy in controlling infections and inflammasome activation in host defense and inflammation. Both were also reported to play important roles in host defense and inflammation on P. aeruginosa pneumonia and sepsis. The cooperation of flagellin and NOD2 in our previous study strongly suggests of the interaction between inflammasome and autophagy (Cell Immunol. 2012;278:1-9). Any significant insult to the gut or alteration to its microbiota is likely to play a role in promoting systemic inflammation and infection in the critically ill population. Therefore, it would seem logical to consider that probiotics may have a role in reducing intestinal colonization by pathogens and thus prevention of infection (pneumonia) and sepsis. Many in vitro and in vivo studies demonstrated the benefit of probiotics on P. aeruginosa infection. However, the major mechanism of action responsible for the clinical effects of probiotics on P. aeruginosa infection are not completely understood, especially on autophagy and inflammasome. Probiotics were observed to regulate autophagic ability and inflammasomes of IECs and mononuclear phagocytes. It suggests the involvement of autophagy and inflammasome in the protective role of probiotics on P. aeruginosa infection. The aims of the project are: The first year: To investigate the effects of probiotics on the autophagy and inflammasome expression of intestinal epithelial cells and macrophage after Pseudomonas aeruginosa infection (In vitro study). The second year: To investigate the protective effects of probiotics on the Pseudomonas aeruginosa pneumonia in mice via regulation of autophagy and inflammasomes of distinctive macrophages (In vivo study). The third year: To investigate the protective effects of probiotics on the gut-derived Pseudomonas aeruginosa sepsis in mice via autophagy and inflammasomes of IECs and macrophages. (In vivo study).

Project ID:PC10508-0351
External Project ID:MOST105-2314-B182-054