title: Capacity of Pneumococci to Activate Macrophage Nuclear Factor κB: Influence on Necroptosis and Pneumonia Severity.
abstract: During pneumococcal pneumonia, antibacterial defense requires the orchestrated expression of innate immunity mediators, initiated by alveolar macrophages and dependent on transcription driven by nuclear factor κB (NF-κB). Such immune pressure may select for pneumococci, which avoid or subvert macrophage NF-κB activation. Analyzing pneumococci collected from children in Massachusetts, we found that the activation of macrophage NF-κB by Streptococcus pneumoniae is highly diverse, with a preponderance of low NF-κB activators that associate particularly with complicated pneumonia. Low NF-κB activators cause more severe lung infections in mice, and they drive macrophages toward an alternate and detrimental cell fate of necroptosis. Both outcomes can be reversed by activation of macrophages with pneumococci that are high NF-κB activators. These results suggest that low NF-κB activation is a virulence property of pneumococci and that the appropriate activation of macrophages, including NF-κB, may hold promise as an adjunct therapeutic avenue for pneumococcal pneumonia.
authors.affiliation: Pulmonary Center.|Department of Microbiology.
authors.forename: Fadie T
authors.initials: FT
authors.lastname: Coleman
authors.affiliation: Pulmonary Center.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Blahna
authors.affiliation: Pulmonary Center.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kamata
authors.affiliation: Pulmonary Center.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Pulmonary Center.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Zabinski
authors.affiliation: Pulmonary Center.|Department of Microbiology.|Deparment of Medicine.
authors.forename: Igor
authors.initials: I
authors.lastname: Kramnik
authors.affiliation: Pulmonary Center.|Deparment of Medicine.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Wilson
authors.affiliation: Pulmonary Center.|Deparment of Medicine.
authors.forename: Darrell N
authors.initials: DN
authors.lastname: Kotton
authors.affiliation: Pulmonary Center.|Deparment of Medicine.|Department of Pathology and Laboratory Medicine.
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Quinton
authors.affiliation: Pulmonary Center.|Deparment of Medicine.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Jones
authors.affiliation: Pulmonary Center.|Pediatric Infectious Disease.
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Pelton
authors.affiliation: Pulmonary Center.|Department of Microbiology.|Deparment of Medicine.|Department of Biochemistry, Boston University School of Medicine, Massachusetts.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mizgerd
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009336:Necrosis / Q000276:immunology* / Q000628:therapy; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000628:therapy; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism; D013296:Streptococcus pneumoniae
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species
keywords: NF-κB; community-acquired pneumonia; innate immunity; macrophages; pneumococcus