Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 178, Issue 6, Pages 2774-2782Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2011.02.038
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Funding
- Division of Intramural Research of the National Institutes of Health/National Institute of Allergy and Infectious Diseases
- National Institutes of Health/National Center on Minority Health and Health Disparities
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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 immnunodeficiency 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 re-challenged 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. (Am J Pathol 2011, 178: 2774-2784. DOI: 10.1016/j.ajpath.2011.02.038)
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