title: Potential role of autophagy in the bactericidal activity of human PMNs for Bacillus anthracis.
abstract: Bacillus anthracis, the causative agent of anthrax, is acquired by mammalian hosts from the environment, as quiescent endospores. These endospores must germinate inside host cells, forming vegetative bacilli, before they can express the virulence factors that enable them to evade host defenses and disseminate throughout the body. While the role of macrophages and dendritic cells in this initial interaction has been established, the role of polymorphonuclear leukocytes (PMNs) has not been adequately defined. We discovered that while B. anthracis 34F2 Sterne endospores germinate poorly within non-activated human PMNs, these phagocytes exhibit rapid microbicidal activity toward the outgrown vegetative bacilli, independent of superoxide and nitric oxide. These findings suggest that a non-free radical pathway kills B. anthracis bacilli. We also find in PMNs an autophagic mechanism of bacterial killing based on the rapid induction of LC-3 conversion, beclin-1 expression, sequestosome 1 (SQSTM1) degradation and inhibition of bactericidal activity by the inhibitor, 3-methyladenine. These findings extend to PMNs an autophagic bactericidal mechanism previously described for other phagocytes.
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA gramacha@medicine.umaryland.edu.
authors.forename: Girish
authors.initials: G
authors.lastname: Ramachandran
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Padmaja
authors.initials: P
authors.lastname: Gade
authors.affiliation: Department of Pharmaceutical Sciences, and the Center for EPR Imaging In Vivo Physiology, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Tsai
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Wuyuan
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Dhananjaya V
authors.initials: DV
authors.lastname: Kalvakolanu
authors.affiliation: Department of Pharmaceutical Sciences, and the Center for EPR Imaging In Vivo Physiology, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Rosen
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Cross
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology* / Q000473:pathology*; D001343:Autophagy; D001408:Bacillus anthracis / Q000276:immunology*; D015153:Blotting, Western; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D050296:Microbial Viability; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology*; D010587:Phagocytosis; D026361:Reactive Nitrogen Species / Q000032:analysis; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species
keywords: B. anthracis; autophagy; neutrophils; phagocytosis