title: Perforin-mediated CTL cytolysis counteracts direct cell-cell spread of Listeria monocytogenes.
abstract: The immune system has evolved various effector cells and functions to combat diverse infectious agents equipped with different virulence strategies. CD8 T cells play a critical role in protective immunity to Listeria monocytogenes (Lm), a bacterium that grows within the host cell cytosol and spreads directly into neighboring cells. The importance of CD8 T cells during Lm infection is currently attributed to the cytosolic niche of this organism, which allows it to evade many aspects of immune surveillance. CTL lysis of infected cells is believed to be an essential protective mechanism, presumably functioning to release intracellular bacteria, although its precise role remains to be fully defined. In this study, we examined the contribution of perforin-mediated CTL cytolysis to protective immunity against recombinant Lm capable of or defective in cell-cell spread. We found that CTL cytolysis is critical for protective immunity to Lm capable of cell-cell spread while protective immunity against spread-defective Lm is largely independent of CTL cytolysis. These results demonstrate that an important function of CTL cytolysis is to counter the microbial virulence strategy of direct cell-cell spread. We propose a model that advances the current view of the role of CTL cytolysis in immunity to intracellular pathogens.
authors.affiliation: Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: Lani R
authors.initials: LR
authors.lastname: San Mateo
authors.forename: Ming Ming
authors.initials: MM
authors.lastname: Chua
authors.forename: Susan R
authors.initials: SR
authors.lastname: Weiss
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011995:Recombination, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000382:microbiology* / Q000821:virology; D014764:Viral Proteins / Q000276:immunology; D014774:Virulence
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D052899:Pore Forming Cytotoxic Proteins; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; D054353:Perforin