Mucosal inducible NO synthase–producing iga+ plasma cells in helicobacter pylori–infected patients

authored by

Laura Neumann, M. Mueller, V. Moos, Frank Heller, Thomas F. Meyer, C. Loddenkemper, C. Bojarski, M. Fehlings, T. Doerner, K. Allers, Toni Aebischer, R. Ignatius, T. Schneider

Abstract

The mucosal immune system is relevant for homeostasis, immunity, and also pathological conditions in the gastrointestinal tract. Inducible NO synthase (iNOS)-dependent production of NO is one of the factors linked to both antimicrobial immunity and pathological conditions. Upregulation of iNOS has been observed in human Helicobacter pylori infection, but the cellular sources of iNOS are ill defined. Key differences in regulation of iNOS expression impair the translation from mouse models to human medicine. To characterize mucosal iNOS-producing leukocytes, biopsy specimens from H. pylori-infected patients, controls, and participants of a vaccination trial were analyzed by immunohistochemistry, along with flow cytometric analyses of lymphocytes for iNOS expression and activity. We newly identified mucosal IgA-producing plasma cells (PCs) as one major iNOS

⁺ cell population in H. pylori-infected patients and confirmed intracellular NO production. Because we did not detect iNOS

⁺ PCs in three distinct infectious diseases, this is not a general feature of mucosal PCs under conditions of infection. Furthermore, numbers of mucosal iNOS

⁺ PCs were elevated in individuals who had cleared experimental H. pylori infection compared with those who had not. Thus, IgA

⁺ PCs expressing iNOS are described for the first time, to our knowledge, in humans. iNOS

⁺ PCs are induced in the course of human H. pylori infection, and their abundance seems to correlate with the clinical course of the infection.

Organisation(s)

Nutrition Physiology and Human Nutrition Section
Institute of Food Science and Human Nutrition

External Organisation(s)

PathoTres Praxis für Pathologie, Berlin
Charité - Universitätsmedizin Berlin
Gastroenterologische Praxis am Rathaus Steglitz
Max Planck Institute for Infection Biology
Robert Koch Institute (RKI)

Type

Article

Journal

The journal of immunology

Volume

197

Pages

1801-1808

No. of pages

ISSN

0022-1767

Publication date

01.09.2016

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Immunology and Allergy, Immunology

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.4049/jimmunol.1501330 (Access: Unknown)