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

Frontiers in Immunology

Marco Alessandrini¹  Karl-Heinz Krause¹  Julien Cachat¹  Stéphanie Hugues¹  Christine Deffert²  Pascale Roux-Lombard²  Audrey Le Gouellec³  Marie-José Stasia³ 

[1] Department of Pathology and Immunology, Geneva University Hospitals (HUG) and Faculty of Medicine, University of Geneva, Geneva, Switzerland;Division of Laboratory Medicine, Department of Genetic and Laboratory Medicine and Department of Medical Specialities, Geneva University Hospitals (HUG) and Faculty of Medicine, University of Geneva, Geneva, Switzerland;Laboratoire BEP, Pôle Biologie, CHU Grenoble Alpes, Grenoble, France;TheREx (Thérapeutique Recombinante Expérimentale), Laboratoire TIMC-IMAG, University Grenoble Alpes, CNRS, Grenoble, France;

关键词: NOX2;    B cells;    T cells;    immunoglobulin;    antigen-presenting cells;    curdlan;   

DOI  :  10.3389/fimmu.2018.01555

来源: DOAJ

【 摘 要 】

Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting from loss of function mutations in the reactive oxygen species generating phagocyte NADPH oxidase (NOX2). CGD patients are prone to infection, but also have an increased susceptibility to autoimmune diseases. The aim of this study was to investigate the role of NOX2 in the regulation of specific immunity. In both CGD patients and NOX2-deficient mice, we observed an alteration in the basal proportions of IgG subtypes. Upon immunization with curdlan—a dectin 1 agonist—NOX2-deficient mice showed increased production of IgG2c compared to controls, and restimulation of lymph node-derived cells led to increased production of IFNγ, but not IL-5, indicative hallmark of an enhanced Th1 response. T cell activation was increased in NOX2-deficient mice and a similar trend was observed in vitro when T cells were co-cultured with NOX2-deficient bone marrow-derived cells. In contrast, no difference in T cell activation was observed when NOX2-deficient T cells were co-cultured with wild-type BMDC. Following stimulation of NOX2-deficient dendritic cells (DCs), no difference in costimulatory molecules was observed, while there was an increase in the release of Th1-driving cytokines. In summary, both CGD patients and CGD mice have an altered IgG subtype distribution, which is associated with an increased IFNγ production. Thus, NOX2 within DCs appears to be an important regulator at the interface of innate and specific immunity, especially after activation of the dectin 1 pathway, limiting immune activation and the development of autoimmunity.

【 授权许可】

Unknown