The Interplay between Autophagy and Inflammasome in Innate Immunity to Govern Salmonella Colitis

  • Huang, Fu-Chen (PI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Salmonella spp. remain major public health problems for the whole world. The incidence of food-borne human infections caused by multi-drug-resistant strains of S. typhimurium increased substantially during 20th century with similar trends being reported from Europe and Taiwan. A better understanding of pathogenesis of these food-borne pathogens is a prerequisite for the design of improved intervention strategies that could reduce the use of antimicrobial agents and drug-resistant Salmonellosis. The autophagy and inflammasome pathways are ancient innate immune mechanisms for controlling invading pathogens. Defects in the autophagy process are associated with a variety of human diseases, including infectious and inflammatroy disease. Recent studies have identified the critical role of inflammasome activation in host defense and inflammation. As a cytosolic pathogen recognition receptor (PRR) complex, the inflammasome both induces and is induced by autophagy through direct interactions with autophagy proteins. The basic understanding of the mutual regulation of inflammasomes and autophagy will be essential for designing therapeutics for intracellular infection or chronic inflammatory diseases. Recent evidence suggests that innate immunity of the host detects and defenses against Salmonella through the activation of autophagy and inflammasomes. NOD2 directs autophagy by recruiting Atg16L1 to the plasma membrane at the bacterial entry site of intestinal epithelial cells and protection from Salmonella infection. Recent data suggest that an effective innate immune response against Salmonella requires the engagement of multiple inflammasomes (e.g. NLRP3, NLRC4, NLRP6). The available data suggest that the main role of inflammasomes is to restrict the replication of the bacteria during the systemic phase of the infection. To our knowledge, the role of NOD2 or ATG16L1 on inflammasome activation after Salmonella infection has not been reported. Previously, we demonstrated that synergistic enhancement on flagellin-induced cytokine production in IECs, possibly caused by flagellin-mediated enhanced NOD2 recruitment into cell membrane. Cytosolic flagellin receptor NLRC4 protects mice against mucosal and systemic challenges with Salmonella. Investigating the interplay between autophagy and inflammasome in governing microbiota and enteric pathogens, and how such interplay regulates the host response to pathogens will provide great insights into understanding intestinal infections and inflammation as well as development of therapeutics for infectious and inflammatory diseases. Therefore, the aims of the project are: (the first year) to investigate the interplay between autophagy and inflammasome of intestinal epithelium in governing Salmonella colitis; (the second year) to investigate the interplay between inflammasome and autophagy of macrophages in governing systemic Salmonella infection; and (the third year) to investigate the effects of probiotics on interplay between inflammasome and autophagy in governing Salmonella colitis and systemic infection.

Project IDs

Project ID:PC10308-1878
External Project ID:MOST103-2314-B182-032
Effective start/end date01/08/1431/07/15


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