title: Delay in Human Neutrophil Constitutive Apoptosis after Infection withKlebsiella pneumoniaeSerotype K1.
abstract: Klebsiella pneumoniaeserotype K1 is a major cause of invasive syndrome defined by liver abscess with metastatic infections at other body sites. This culprit is known to be resistant to neutrophil phagocytosis and bactericidal activity. We hypothesized thatK. pneumoniaeserotype K1 might regulate neutrophil apoptosis and enhance the survival of the infected neutrophils that might serve as a vector for dissemination of the bacteria. Two serotypes ofK. pneumoniae, KP-M1 isolated from a patient with liver abscess and DT-X (an acapsular mutant strain of KP-M1), were used to infect human neutrophils. The infected neutrophils were examined for their cytotoxicity, annexin V staining, proteins, DNA fragmentation, cytokine production, and viability that are involved in apoptosis. We found that KP-M1 was not destroyed and the ingested bacteria survived within neutrophils. While the uninfected neutrophils became apoptotic within 10 h, the neutrophils infected with KP-M1 could survive up to 24 h post infection. Constitutive apoptosis of KP-M1-infected neutrophils was significantly delayed compared to that of DT-X-infected or uninfected neutrophils (p< 0.01). KP-M1 modulated the anti-apoptotic effects by down-regulating the ratio of Bax to Bcl-2 and Mcl-1, and then delayed caspase-3 activation in the neutrophils, which was accompanied by inducing the anti-apoptotic cytokine, IL-8. These data suggest thatK. pneumoniaeserotype K1 can prolong the lifespan of infected neutrophils by delaying constitutive apoptosis within the first several hours of infection.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalKaohsiung, Taiwan; Chang Gung University College of MedicineKaohsiung, Taiwan.
authors.forename: Chen-Hsiang
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Chang Gung University College of MedicineKaohsiung, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalKaohsiung, Taiwan.
authors.forename: Seng-Kee
authors.initials: SK
authors.lastname: Chuah
authors.affiliation: Chang Gung University College of MedicineKaohsiung, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalKaohsiung, Taiwan.
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Tai
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalKaohsiung, Taiwan; Chang Gung University College of MedicineKaohsiung, Taiwan.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalKaohsiung, Taiwan; Chang Gung University College of MedicineKaohsiung, Taiwan.
authors.forename: Fang-Ju
authors.initials: FJ
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007710:Klebsiella Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000145:classification* / Q000502:physiology*; D050296:Microbial Viability / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D010587:Phagocytosis / Q000276:immunology; D065288:Serogroup; D014774:Virulence
chemical_list: D016207:Cytokines; D053148:Caspase 3
keywords: capsular polysaccharide; innate immunity; metastatic infection; pathogenesis; virulence