Elmo-1 Regulates the Induction of Autophagy and Bacterial Clearance During Salmonella Infection

Macrophages are specialized phagocytic cells involved in clearing invading pathogens by phagolysosomal and autophagic degradation. Earlier, we reported that Brain Angiogenesis Inhibitor 1 (BAI1) recognizes bacterial lipopolysaccharide (LPS). BAI1 binds to Engulfment and Cell Motility 1 (ELMO1) that mediates the engulfment of Salmonella and regulates inflammatory responses. Here, we hypothesize that BAI1-ELMO1 pathway plays a crucial role in bacterial clearance by modulating host cell immune responses. Salmonella infection in J774 increases accumulation of an autophagic marker LC3B in an ELMO1-dependent manner. Silencing ATG5 in ELMO1-knockdown cells confirms that ATG5 is essential for ELMO1-mediated LC3B regulation. This result indicates that ELMO1 regulates conventional autophagy. Subcellular fractionation shows that like BAI1, ELMO1 is present in phagosomes. Furthermore, we show that the lysosomal environment of ELMO1-knockdown cells is more acidic and proteolytic in nature as compared to the empty vector-transfected cells. In addition, we confirm that faster recruitment of the Early Endosomal Antigen 1 (EEA1) and the Lysosomal marker LAMP1 occurs in ELMO1-shRNA cells. These results suggest there is an interrelationship between autophagic regulation and the clearance of pathogens through ELMO1-mediated events. Taken together, we conclude that ELMO1 is an important modulator for the clearance of enteric pathogens by controlling cellular autophagy.