IgG Subclass-Dependent Pulmonary Antigen Retention during Acute IgG-Dependent Systemic Anaphylaxis in Mice.

Autor:	Todorova B; Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Université de Paris, INSERM UMR1222, Paris, France., Godon O; Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Université de Paris, INSERM UMR1222, Paris, France., Conde E; Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Université de Paris, INSERM UMR1222, Paris, France., Gillis CM; Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Université de Paris, INSERM UMR1222, Paris, France., Iannascoli B; Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Université de Paris, INSERM UMR1222, Paris, France., Richard-Le Goff O; Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Université de Paris, INSERM UMR1222, Paris, France., Fiole D; Unité Biothérapies Anti-Infectieuses et Immunité, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, Brétigny sur Orge, France.; Unit of Human Histopathology and Animal Models, Institut Pasteur, Université de Paris, Paris, France., Roumenina LT; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France., Leusen JHW; Center for Translational Immunology, UMC Utrecht, Utrecht, the Netherlands., Murphy AJ; Regeneron Pharmaceuticals, Inc., Tarrytown, NY; and., Macdonald LE; Regeneron Pharmaceuticals, Inc., Tarrytown, NY; and., Reber LL; Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Université de Paris, INSERM UMR1222, Paris, France.; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291, CNRS UMR5051, University Toulouse III, Toulouse, France., Jönsson F; Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Université de Paris, INSERM UMR1222, Paris, France., Bruhns P; Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Université de Paris, INSERM UMR1222, Paris, France; bruhns@pasteur.fr.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2022 Oct 01; Vol. 209 (7), pp. 1243-1251. Date of Electronic Publication: 2022 Sep 07.
DOI:	10.4049/jimmunol.2200234
Abstrakt:	Mouse models of active systemic anaphylaxis rely predominantly on IgG Abs forming IgG-allergen immune complexes that induce IgG receptor-expressing neutrophils and monocytes/macrophages to release potent mediators, leading to systemic effects. Whether anaphylaxis initiates locally or systemically remains unknown. In this study, we aimed at identifying the anatomical location of IgG-allergen immune complexes during anaphylaxis. Active systemic anaphylaxis was induced following immunization with BSA and i.v. challenge with fluorescently labeled BSA. Ag retention across different organs was examined using whole-body fluorescence imaging, comparing immunized and naive animals. Various mouse models and in vivo deletion strategies were employed to determine the contribution of IgG receptors, complement component C1q, myeloid cell types, and anaphylaxis mediators. We found that following challenge, Ag diffused systemically, but specifically accumulated in the lungs of mice sensitized to that Ag, where it formed large Ab-dependent aggregates in the vasculature. Ag retention in the lungs did not rely on IgG receptors, C1q, neutrophils, or macrophages. IgG2a-mediated, but neither IgG1- nor IgG2b-mediated, passive systemic anaphylaxis led to Ag retention in the lung. Neutrophils and monocytes significantly accumulated in the lungs after challenge and captured high amounts of Ag, which led to downmodulation of surface IgG receptors and triggered their activation. Thus, within minutes of systemic injection in sensitized mice, Ag formed aggregates in the lung and liver vasculature, but accumulated specifically and dose-dependently in the lung. Neutrophils and monocytes recruited to the lung captured Ag and became activated. However, Ag aggregation in the lung vasculature was not necessary for anaphylaxis induction. (Copyright © 2022 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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