Defective apoptotic cell clearance activates innate immune response to protect Caenorhabditis elegans against pathogenic bacteria

Abstract

Appropriate clearance of dead cells generated by apoptosis is critical to the development of multicellular organisms and tissue homeostasis. In mammals, the removal of apoptotic cell is mediated by polarized monocyte/macrophage populations of the innate immune system. The innate immune system is essential for anti-viral and anti-microbial defense. However, our current understanding of the relationship between apoptotic cell clearance and the innate immune response has remained rather limited. Here, we study how apoptotic cell clearance programs contribute to the innate immune response in C. elegans. We find apoptotic cell clearance mutant worms are more resistant to pathogenic bacteria of Pseudomonas aeruginosa PA14 and Salmonella typhimurium SL1344 due to significant upregulation of innate immune-dependent pathogen response genes. In addition, genetic epistasis analysis indicates that defects in apoptotic cell clearance can activate the innate immune response through PMK-1 p38 MAPK and MPK-1/ERK MAPK pathways in C. elegans. Taken together, our results provide evidence that insufficient clearance of apoptotic cell can protect Caenorhabditis elegans from bacterial infection through innate immune response activation.

Keywords

• c. elegans
• apoptosis
• apoptotic cell clearance
• innate immune
• lysosomes