Fascin confers resistance to Listeria infection in dendritic cells.
Ag-presenting dendritic cells (DCs) must survive bacterial infection to present Ag information to naive T cells. The greater ability of DCs' host defense is evident from the report that DCs are more resistant to Listeria monocytogenes than macrophages. However, the molecular mechanism of this resistance is unclear. We found that Listeria replicate more slowly in wild-type DCs compared with fascin1 knockout DCs. This finding is significant because fascin1, an actin-bundling protein, is specifically and greatly induced upon maturation of dendritic cells, but not other blood cells, including macrophages and neutrophils. Infection by Listeria makes phagosomes more acidic in wild-type DCs than in fascin1 knockout DCs, suggesting that fascin1 facilitates phagolysosomal fusion for killing of phagocytosed Listeria. We further found that fascin1 binds to LC3, an autophagosome marker, both in vivo and in vitro. Listeria are associated with LC3 to a greater extent in wild-type DCs than in fascin1 knockout DCs, suggesting that fascin1 facilitates autophagy for eradication of cytoplasmic Listeria. Taken together, our results suggest that fascin1 plays critical roles in the survival of DCs during Listeria infection, allowing DCs to function in innate and adaptive immunity.
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854.
Fumio
F
Matsumura
Yoshihiko
Y
Yamakita
Val
V
Starovoytov
Shigeko
S
Yamashiro
D000818:Animals; D001343:Autophagy / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology* / Q000648:ultrastructure; D007113:Immunity, Innate; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000502:physiology*; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010588:Phagosomes / Q000737:chemistry / Q000382:microbiology / Q000502:physiology; D011485:Protein Binding; D018035:Receptors, Odorant; D014617:Vacuoles / Q000737:chemistry / Q000502:physiology
D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D018035:Receptors, Odorant; C480860:Map1lc3b protein, mouse; C544141:Olfr73 protein, mouse