title: Comparison of pulmonary inflammatory and antioxidant responses to intranasal live and heat-killed Streptococcus pneumoniae in mice.
abstract: Inflammatory and antioxidant responses, in male C57Bl6J mice, to single intranasal inoculations with live or heat-killed Streptococcus pneumoniae were studied in order to tease out differences in responses. Heat-killed bacteria elicited weak lung neutrophil infiltration and raised concentrations (peak 6-8 h), in serum or lung tissue, of CXCL1 and 2, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and granulocyte-macrophage-colony stimulating factor, with later increases in CCL2 and IL-1β. Live bacteria induced profound pulmonary neutrophil infiltration and acute chemokine/cytokine elevations. After 72-96 h, live S. pneumoniae induced a delayed rise in chemokines CXCL2 and CCL2, preceded by increases in TNFα, IL-1β, and IL-6 and mononuclear infiltration of lungs. With both live and heat-killed bacteria, alveolar epithelial type II cells and alveolar macrophages were the main sources of TNFα and IL-1β. Only live bacteria caused an acute decrease in lung glutathione peroxidase, an increase in superoxide dismutase, and a sustained increase in serum amyloid protein A. Acute innate immune responses to live and heat-killed S. pneumoniae are similar. In response to live bacteria, inflammation is greater, accompanied by changes in antioxidant enzymes and has an additional, later mononuclear component.
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovia 29, HR, 10000, Zagreb, Croatia. Miroslava.DominisKramaric@glpg.com
authors.forename: Miroslava
authors.initials: M
authors.lastname: Dominis-Kramarić
authors.forename: Martina
authors.initials: M
authors.lastname: Bosnar
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Kelnerić
authors.forename: Ines
authors.initials: I
authors.lastname: Glojnarić
authors.forename: Snježana
authors.initials: S
authors.lastname: Cužić
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parnham
authors.forename: Vesna
authors.initials: V
authors.lastname: Eraković Haber
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D058491:Bacterial Load; D054360:Chemokine CXCL1 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006358:Hot Temperature; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase