PMID- 27440002 OWN - NLM STAT- MEDLINE DCOM- 20171229 LR - 20200902 IS - 1554-8635 (Electronic) IS - 1554-8627 (Print) IS - 1554-8627 (Linking) VI - 12 IP - 9 DP - 2016 Sep TI - Extracellular stimulation of VSIG4/complement receptor Ig suppresses intracellular bacterial infection by inducing autophagy. PG - 1647-59 LID - 10.1080/15548627.2016.1196314 [doi] AB - VSIG4/CRIg (V-set and immunoglobulin domain containing 4) is a transmembrane receptor of the immunoglobulin superfamily that is expressed specifically on macrophages and mature dendritic cells. VSIG4 signaling accelerates phagocytosis of C3-opsonized bacteria, thereby efficiently clearing pathogens within macrophages. We found that VSIG4 signaling triggered by C3-opsonized Listeria (opLM) or by agonistic anti-VSIG4 monoclonal antibody (mAb) induced macrophages to form autophagosomes. VSIG4-induced autophagosomes were selectively colocalized with the intracellular LM while starvation-induced autophagosomes were not. Consistent with these results, the frequency of autophagosomes induced by infection with opLM was lower in VSIG4-deficient bone marrow-derived macrophages (BMDMs) than in WT BMDMs. Furthermore, when VSIG4 molecules were overexpressed in HeLa cells, which are non-macrophage cells, VSIG4 triggering led to efficient uptake of LM, autophagosome formation, and killing of the infected LM. These findings suggest that VSIG4 signaling not only promotes rapid phagocytosis and killing of C3-opsonized intracellular bacteria, as previously reported, but also induces autophagosome formation, eliminating the LM that have escaped from phagosomes. We conclude that VSIG4 signaling provides an anti-immune evasion mechanism that prevents the outgrowth of intracellular bacteria in macrophages. FAU - Kim, Kwang H AU - Kim KH AD - a Eutilex , The Catholic University School of Medicine Seoul , Korea. FAU - Choi, Beom K AU - Choi BK AD - b Cancer Immunology Branch , Division of Cancer Biology, National Cancer Center , Goyang , Korea. FAU - Kim, Young H AU - Kim YH AD - c Immune Cell Production Unit , Program for Immunotherapeutic Research, National Cancer Center , Goyang , Korea. FAU - Han, Chungyong AU - Han C AD - b Cancer Immunology Branch , Division of Cancer Biology, National Cancer Center , Goyang , Korea. FAU - Oh, Ho S AU - Oh HS AD - b Cancer Immunology Branch , Division of Cancer Biology, National Cancer Center , Goyang , Korea. FAU - Lee, Don G AU - Lee DG AD - b Cancer Immunology Branch , Division of Cancer Biology, National Cancer Center , Goyang , Korea. FAU - Kwon, Byoung S AU - Kwon BS AD - a Eutilex , The Catholic University School of Medicine Seoul , Korea. AD - b Cancer Immunology Branch , Division of Cancer Biology, National Cancer Center , Goyang , Korea. AD - d Department of Medicine , Tulane University Health Sciences Center , New Orleans , LA , USA. LA - eng PT - Journal Article DEP - 20160720 PL - United States TA - Autophagy JT - Autophagy JID - 101265188 RN - 0 (Antibodies, Monoclonal) RN - 0 (Atg5 protein, mouse) RN - 0 (Autophagy-Related Protein 5) RN - 0 (Immunoglobulin G) RN - 0 (Receptors, Complement) RN - 0 (VSIG4 protein, human) RN - 0 (VSIG4 protein, mouse) SB - IM MH - Animals MH - Antibodies, Monoclonal/immunology MH - Autophagosomes/metabolism MH - *Autophagy MH - Autophagy-Related Protein 5/genetics MH - Bacterial Infections/*immunology MH - Bone Marrow Cells/cytology MH - Cell Line MH - HeLa Cells MH - Humans MH - Immunoglobulin G/immunology MH - Listeria/metabolism MH - Macrophages/cytology/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Phagocytosis/immunology MH - Phagosomes/metabolism MH - Receptors, Complement/*metabolism MH - Signal Transduction PMC - PMC5082771 OTO - NOTNLM OT - CRIg OT - LC3B OT - Listeria OT - VSIG4 OT - autophagy OT - macrophage OT - ubiquitin EDAT- 2016/07/22 06:00 MHDA- 2017/12/30 06:00 PMCR- 2017/07/20 CRDT- 2016/07/22 06:00 PHST- 2016/07/22 06:00 [entrez] PHST- 2016/07/22 06:00 [pubmed] PHST- 2017/12/30 06:00 [medline] PHST- 2017/07/20 00:00 [pmc-release] AID - 1196314 [pii] AID - 10.1080/15548627.2016.1196314 [doi] PST - ppublish SO - Autophagy. 2016 Sep;12(9):1647-59. doi: 10.1080/15548627.2016.1196314. Epub 2016 Jul 20.