Abstract
Listeria monocytogenes (L. monocytogenes), which is a facultative intracellular bacterial pathogen that causes listeriosis, is widely used to study the mammalian immune response to infection. After phagocytosis by professional phagocytes, L. monocytogenes is initially contained within phagosomes, which mature into phagolysosomes, where the bacteria are degraded. Although phagocytosis and subsequent phagosome maturation is essential for the clearance of infectious microbial pathogens, the underlying regulatory mechanisms are still unclear. SNX10 (Sorting nexin 10) has the simplest structure of the SNX family and has been reported to regulate endosomal morphology, which might be crucial for macrophage function, including phagocytosis and digestion of pathogens, inflammatory response, and antigen presentation. Our results showed that SNX10 expression was upregulated following L. monocytogenes infection in macrophages. It was also revealed that SNX10 promoted phagosome maturation by recruiting the Mon1-Ccz1 complex to endosomes and phagosomes. As a result, SNX10 deficiency decreased the bacterial killing ability of macrophages, and SNX10-deficient mice showed increased susceptibility to L. monocytogenes infection in vivo. Thus, this study revealed an essential role of SNX10 in controlling bacterial infection.
Highlights
Macrophages are important immune cells of the innate immune system that participate in the host defense against bacterial pathogens
To investigate the function of SNX10 in macrophages, we examined its expression in bone marrow-derived macrophages (BMDMs) after stimulation with different Toll-like receptors (TLRs) ligands
Similar results were observed in both types of bacterial infection; the mRNA expression of Snx10 in BMDMs was significantly upregulated after infection with heat-killed L. monocytogenes (HKLM), heat-killed E. coli (HKEC) and heat-killed S. typhimurium (HKST) but SNX10 upregulation after infection with VSV(vesicular stomatitis virus) was negligible (Figure 1D)
Summary
Macrophages are important immune cells of the innate immune system that participate in the host defense against bacterial pathogens. They mediate bacterial clearance by internalizing bacteria into phagosomes, which fuse with lysosomes to kill bacteria [1]. Following ingestion of various contaminated food products, L. monocytogenes crosses the intestinal barrier by invading the intestinal epithelium and reaches internal organs, such as the liver and spleen, via the lymphoid system and blood circulation [2, 3]. After the bacteria enter host cells, L. monocytogenes can escape from these compartments prior to lysosomal fusion to avoid being killed in phagosomes. Activated macrophages kill L. monocytogenes by blocking this phagosomal escape [4]. Phagosome maturation may affect the vacuolar escape of L. monocytogenes: slower maturation will allow more time for L. monocytogenes to escape
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
