Role of P47phox in Antigen-presenting Cell-mediated Regulation of Humoral Immunity in Mice

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2011 Jun 7

PMID 21641399

Citations 8

Authors

Sam Vasilevsky

Qi Liu

Sherry M Koontz

Robin Kastenmayer

Katherine Shea

Sharon H Jackson

Affiliations

Soon will be listed here.

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.

Citing Articles

Dynamic Activation of NADPH Oxidases in Immune Responses Modulates Differentiation, Function, and Lifespan of Plasma Cells.

Bucheli O, Rodrigues D, Ulbricht C, Hauser A, Eyer K Eur J Immunol. 2025; 55(2):e202350975.

PMID: 39931760 PMC: 11811814. DOI: 10.1002/eji.202350975.

Beyond the Extra Respiration of Phagocytosis: NADPH Oxidase 2 in Adaptive Immunity and Inflammation.

Mortimer P, Mc Intyre S, Thomas D Front Immunol. 2021; 12:733918.

PMID: 34539670 PMC: 8440999. DOI: 10.3389/fimmu.2021.733918.

Altered Humoral Immune Responses and IgG Subtypes in NOX2-Deficient Mice and Patients: A Key Role for NOX2 in Antigen-Presenting Cells.

Cachat J, Deffert C, Alessandrini M, Roux-Lombard P, Le Gouellec A, Stasia M Front Immunol. 2018; 9:1555.

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P47phox-/- mice are compromised in expansion and activation of CD8+ T cells and susceptible to Trypanosoma cruzi infection.

Dhiman M, Garg N PLoS Pathog. 2014; 10(12):e1004516.

PMID: 25474113 PMC: 4256457. DOI: 10.1371/journal.ppat.1004516.

An AAVS1-targeted minigene platform for correction of iPSCs from all five types of chronic granulomatous disease.

Merling R, Sweeney C, Chu J, Bodansky A, Choi U, Priel D Mol Ther. 2014; 23(1):147-57.

PMID: 25288370 PMC: 4426805. DOI: 10.1038/mt.2014.195.

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