title: Chlamydia pneumoniae multiply in neutrophil granulocytes and delay their spontaneous apoptosis.
abstract: The obligate intracellular bacterial pathogen Chlamydia pneumoniae (Cp) is responsible for a range of human diseases, including acute respiratory infection. Although experimental intratracheal infection with Cp results in a massive recruitment of neutrophil granulocytes (polymorphonuclear neutrophils (PMN)), the role of these cells in the defense against Cp is unclear. In this study the interactions of PMN with Cp were investigated. In vitro coincubation experiments showed that human granulocytes were able to internalize Chlamydia in an opsonin-independent manner. Importantly, phagocytosed Cp were not killed; the ingested bacteria survived and multiplied within PMN. Although uninfected granulocytes became apoptotic within 10 h, infected PMN survived up to 90 h. Coincubation with Cp significantly decreased the ratio of apoptotic PMN, as detected by morphological analysis, annexin V, and TUNEL staining. The observed antiapoptotic effect was associated with a markedly lower level of procaspase-3 processing and, consequently, reduced caspase-3 activity in infected PMN. LPS was found as a major, but not exclusive, component responsible for the observed antiapoptotic effect. Chlamydia LPS affected PMN apoptosis both by acting directly on the cells and by inducing the autocrine production of the antiapoptotic cytokine IL-8. These data show that, in contrast to other microbial pathogens that drive phagocytes into apoptosis to escape killing, Cp can extend the life span of neutrophil granulocytes, making them suitable host cells for survival and multiplication within the first hours/days after infection.
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany. zandbergen@hygiene.ukl.mu-luebeck.de
authors.forename: Ger
authors.initials: G
authors.lastname: van Zandbergen
authors.forename: Jens
authors.initials: J
authors.lastname: Gieffers
authors.forename: Henning
authors.initials: H
authors.lastname: Kothe
authors.forename: Jan
authors.initials: J
authors.lastname: Rupp
authors.forename: Annalena
authors.initials: A
authors.lastname: Bollinger
authors.forename: Eresso
authors.initials: E
authors.lastname: Aga
authors.forename: Matthias
authors.initials: M
authors.lastname: Klinger
authors.forename: Helmut
authors.initials: H
authors.lastname: Brade
authors.forename: Klaus
authors.initials: K
authors.lastname: Dalhoff
authors.forename: Matthias
authors.initials: M
authors.lastname: Maass
authors.forename: Werner
authors.initials: W
authors.lastname: Solbach
authors.forename: Tamás
authors.initials: T
authors.lastname: Laskay
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002474:Cell-Free System / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D016993:Chlamydophila pneumoniae / Q000254:growth & development* / Q000472:pathogenicity; D018920:Coculture Techniques; D015536:Down-Regulation / Q000276:immunology; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism / Q000494:pharmacology; D007424:Intracellular Fluid / Q000276:immunology / Q000382:microbiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology*; D010587:Phagocytosis / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
chemical_list: D061945:Caspase Inhibitors; D004792:Enzyme Precursors; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases