title: Mechanisms of apoptosis inhibition in Chlamydia pneumoniae-infected neutrophils.
abstract: The obligatory intracellular bacterium Chlamydia pneumoniae (C. pneumoniae) can survive and multiply in neutrophil granulocytes. Since neutrophils are short living cells, inhibition of neutrophil apoptosis appears to play a major role in the productive infection of neutrophils by C. pneumoniae. In the present study, we have investigated which survival pathways and which events of the apoptotic process are modulated in C. pneumoniae-infected neutrophils. All infection experiments were carried out using primary human neutrophils in vitro. We show that infection with C. pneumoniae activates PI3K/Akt as well as the ERK1/2 and p38 MAP kinases and present evidence that activation of the PI3K/Akt and ERK1/2 pathways are essential to initiate the apoptosis delay in C. pneumoniae-infected neutrophils. Both the PI3K/Akt and ERK1/2 pathways are involved in the maintained expression of the anti-apoptotic protein Mcl-1. In addition, we also showed that the PI3K/Akt pathway leads to the activation of NF-κB-dependent release of IL-8 by infected neutrophils. Infection with C. pneumoniae activates the PI3K/Akt and ERK1/2 MAPK survival pathways in neutrophils, induces the NF-κB dependent release of IL-8 and leads to the maintenance of Mcl-1 expression in neutrophils.
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Lübeck, German Center for Infection Research (DZIF), Ratzeburger Allee 160, D-23538 Lübeck, Germany. Electronic address: arup.s2010@gmail.com.
authors.forename: Arup
authors.initials: A
authors.lastname: Sarkar
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Lübeck, German Center for Infection Research (DZIF), Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Möller
authors.affiliation: National Institute of Science Education and Research, School of Biological Sciences, Bhubaneswar 751005, Odisha, India.
authors.forename: Asima
authors.initials: A
authors.lastname: Bhattacharyya
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Lübeck, German Center for Infection Research (DZIF), Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Behnen
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Lübeck, German Center for Infection Research (DZIF), Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rupp
authors.affiliation: Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, D-63225 Langen, Germany.
authors.forename: Ger
authors.initials: G
authors.lastname: van Zandbergen
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Lübeck, German Center for Infection Research (DZIF), Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Solbach
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Lübeck, German Center for Infection Research (DZIF), Ratzeburger Allee 160, D-23538 Lübeck, Germany. Electronic address: Tamas.Laskay@uk-sh.de.
authors.forename: Tamás
authors.initials: T
authors.lastname: Laskay
mesh_terms: D017209:Apoptosis; D016993:Chlamydophila pneumoniae / Q000254:growth & development*; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000382:microbiology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D016209:Interleukin-8; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: ERK1/2; IL-8; Mcl-1; NF-κB; PI3-K/Akt