title: Apoptotic cells enhance pathogenesis of Listeria monocytogenes.
abstract: Infections by pathogenic microorganisms elicit host immune responses, which crucially limit those infections. Pathogens employ various strategies to evade host immunity. We have identified the exploitation of the repertoire of potent immunosuppressive responses elicited normally by apoptotic cells ("Innate Apoptotic Immunity"; IAI) as one of these strategies. In the case of Listeria monocytogenes, an environmentally ubiquitous, foodborne bacterial pathogen capable of causing life-threatening invasive disease in immunocompromised and elderly individuals, the induction of host cell apoptosis appears to play an important role in pathogenesis. Previous studies have documented extensive lymphocyte apoptosis resulting from L. monocytogenes infection and demonstrated paradoxically that lymphocyte-deficient animals exhibit diminished susceptibility to listerial pathogenicity. We speculated that the triggering of IAI following the induction of host cell apoptosis was responsible for enhanced pathogenesis, and that the administration of exogenous apoptotic cells would serve to exert this effect. Importantly, apoptotic cells, which are not susceptible to L. monocytogenes infection, do not provide a niche for bacterial replication. Our experiments confirm that apoptotic cells, including exogenous apoptotic cells induced to die independently of the pathogen, specifically enhance pathogenesis. The recognition of a role of apoptotic cells and Innate Apoptotic Immunity in microbial pathogenesis provides an intriguing and novel insight for therapeutic approaches for the control of pathogenic infections.
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612, United States.
authors.forename: Goutham
authors.initials: G
authors.lastname: Pattabiraman
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612, United States.
authors.forename: Karol
authors.initials: K
authors.lastname: Palasiewicz
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612, United States.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Visvabharathy
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612, United States.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Freitag
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612, United States. Electronic address: duck@uic.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Ucker
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008089:Listeria monocytogenes / Q000276:immunology / Q000472:pathogenicity*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D008214:Lymphocytes / Q000276:immunology; D008810:Mice, Inbred C57BL; D015398:Signal Transduction
chemical_list: D016207:Cytokines
keywords: Apoptosis; Immune suppression; Inflammation; Innate immunity; Pathogenesis