Dendritic cells inhibit the progression of Listeria monocytogenes intracellular infection by retaining bacteria in major histocompatibility complex class II-rich phagosomes and by limiting cytosolic growth.
Dendritic cells (DC) provide a suboptimal niche for the growth of Listeria monocytogenes, a facultative intracellular bacterial pathogen of immunocompromised and pregnant hosts. This is due in part to a failure of large numbers of bacteria to escape to the cytosol, an essential step in the intracellular life cycle that is mediated by listeriolysin O (LLO). Here, we demonstrate that wild-type bacteria that failed to enter the cytosol of bone marrow-derived DC were retained in a LAMP2+ compartment. An isogenic L. monocytogenes strain that produces an LLO protein with reduced pore-forming activity had a severe escape and growth phenotype in DC. Few mutant bacteria entered the cytosol in the first 2 h and were instead found in LAMP2+, major histocompatibility complex class II+ (MHC-II+) H2-DM vesicles characteristic of MHC-II antigen loading compartments (MIIC). In contrast, the mutant had a minor phenotype in bone marrow-derived macrophages (BMM) despite the reduced LLO activity. In the first hour, DC phagosomes acidified to a pH that was, on average, half a point higher than that of BMM phagosomes. Unlike BMM, L. monocytogenes growth in DC was minimal after 5 h, and consequently, DC remained viable and matured late in infection. Taken together, the data are consistent with a model in which phagosomal maturation events associated with the acquisition of MHC-II molecules present a suboptimal environment for L. monocytogenes escape to the DC cytosol, possibly by limiting the activity of LLO. This, in combination with an undefined mechanism that controls bacterial growth late in infection, promotes DC survival during the critical maturation response.
Westcott
Marlena M
MM
Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Henry
Curtis J
CJ
Amis
Jacqueline E
JE
Hiltbold
Elizabeth M
EM
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology*; D005260:Female; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005802:Genes, MHC Class II / Q000276:immunology; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D052119:Lysosomal-Associated Membrane Protein 2 / Q000276:immunology; D008247:Lysosomes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010588:Phagosomes / Q000276:immunology / Q000382:microbiology*; D013388:Succinimides
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D005452:Fluoresceins; D005456:Fluorescent Dyes; D052119:Lysosomal-Associated Membrane Protein 2; D013388:Succinimides
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