title: Role of p47phox in antigen-presenting cell-mediated regulation of humoral immunity in mice.
abstract: Microbial-induced inflammation is important for eliciting humoral immunity. Genetic defects of NADPH oxidase 2-based proteins interrupt phagocyte superoxide generation and are the basis for the human immunodeficiency chronic granulomatous disease (CGD). Hyperinflammation is also a significant clinical manifestation of CGD. Herein, we evaluated humoral immunity in the phagocyte oxidase p47(phox)-deficient model of CGD and found that UV-inactivated Streptococcus pneumoniae and Listeria monocytogenes (Lm) elicited higher specific antibody (Ab) titers in p47(phox-/-) mice than wild-type (WT) mice. Both organisms elicited robust and distinct antigen-presenting cell maturation phenotypes, including IL-12 hypersecretion, and higher major histocompatibility complex II and costimulatory protein expression in Lm-stimulated p47(phox-/-) dendritic cells (DCs) relative to WT DCs. Furthermore, p47(phox-/-) DCs pulsed with Lm and adoptively transferred into naïve WT mice elicited Ab titers, whereas Lm-pulsed WT DCs did not elicit these titers. The observed robust p47(phox-/-) mouse humoral response was recapitulated with live Lm and sustained in vivo in p47(phox-/-) mice. Notably, anti-serum samples from p47(phox-/-) mice that survived secondary Lm infection were protective in WT and p47(phox-/-) mice that were rechallenged with secondary lethal Lm infection. These findings demonstrate a novel benefit of NADPH oxidase 2 deficiency (ie, dependent inflammation in antigen-presenting cell-mediated humoral immunity) and that anti-Lm Ab can be protective in an immunodeficient CGD host.
authors.affiliation: Molecular Trafficking Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Vasilevsky
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Sherry M
authors.initials: SM
authors.lastname: Koontz
authors.forename: Robin
authors.initials: R
authors.lastname: Kastenmayer
authors.forename: Katherine
authors.initials: K
authors.lastname: Shea
authors.forename: Sharon H
authors.initials: SH
authors.lastname: Jackson
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000097:blood / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000172:deficiency / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000276:immunology
chemical_list: D016207:Cytokines; D007106:Immune Sera; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1