title: Identification of a detrimental role for NK cells in pneumococcal pneumonia and sepsis in immunocompromised hosts.
abstract: Gram-positive sepsis is a major disease problem. However, the contribution of various immune cell types to pathogenesis remains unclear. By infecting scid and wild type BALB/c mice with Streptococcus pneumoniae we have found a situation in which natural killer (NK) cells can play a detrimental role in the response to infection. scid mice were found to be significantly more susceptible to local and systemic pneumococcal infection than controls; they had significantly higher bacterial loads, elevated inflammatory responses and more widespread lung pathology. Interestingly, depletion of NK cells in scid mice resulted in significantly lower bacteraemia and inflammatory cytokine production. Infection with pneumococci deficient in pneumolysin revealed the toxin was involved in cytokine production. Overall results indicate that elevated NK cell activity during pneumococcal pneumonia amplifies pulmonary and systemic inflammation, increases bacteraemia and results in poor outcome.
authors.affiliation: Division of Infection and Immunity, IBLS, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Alison R
authors.initials: AR
authors.lastname: Kerr
authors.forename: Lea Ann S
authors.initials: LA
authors.lastname: Kirkham
authors.forename: Aras
authors.initials: A
authors.lastname: Kadioglu
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
authors.forename: Paul
authors.initials: P
authors.lastname: Garside
authors.forename: Hal
authors.initials: H
authors.lastname: Thompson
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016867:Immunocompromised Host / Q000276:immunology*; D007694:Killer Cells, Natural / Q000502:physiology*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000473:pathology; D018805:Sepsis / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000502:physiology; D013301:Streptolysins / Q000235:genetics / Q000502:physiology; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae