| First Author | Vasilevsky S | Year | 2011 |
| Journal | Am J Pathol | Volume | 178 |
| Issue | 6 | Pages | 2774-82 |
| PubMed ID | 21641399 | Mgi Jnum | J:173472 |
| Mgi Id | MGI:5014126 | Doi | 10.1016/j.ajpath.2011.02.038 |
| Citation | Vasilevsky S, et al. (2011) Role of p47phox in Antigen-Presenting Cell-Mediated Regulation of Humoral Immunity in Mice. Am J Pathol 178(6):2774-82 |
| abstractText | 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 naive 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. |
