Presentation of Listeria monocytogenes to CD8+ T cells requires secretion of hemolysin and intracellular bacterial growth.
Cell-mediated immunity to Listeria monocytogenes (LM) involves both CD4+ and CD8+ T cell responses. An important virulence factor in the pathogenesis of infection and development of protective immunity to LM is secretion of the sulfhydryl-activated hemolysin (Hly), listeriolysin. Listeria secretion of Hly allows LM to escape the endosomal compartment and enter the cytosol of the cell where intracellular growth can occur. We developed a system using bone marrow macrophages cultured in CSF-1 or IFN-gamma for comparing the response of CD4+ or CD8+ T cells to heat-killed, live Hly-, and live Hly+ LM. Macrophages grown in CSF were permissive for intracellular growth of Hly+ but not Hly- LM. CD8+ T cells recognized Hly+ LM but not HK or Hly- LM pulsed macrophages. However, CD4+ T cells recognized all three Listeria preparations fed to IFN-gamma-treated macrophages. These results suggest that both heat-killed LM and live LM efficiently enter the exogenous pathway for class II Ag processing and presentation. In contrast, only Hly+ LM activates the class I pathway, probably as a result of Hly+ bacterial replication within the cytosolic compartment.
Brunt
L M
LM
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Portnoy
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DA
Unanue
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D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D006460:Hemolysin Proteins / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D006460:Hemolysin Proteins; D007371:Interferon-gamma