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Acellular Bordetella pertussis vaccine enhances mucosal interleukin-10 production, induces apoptosis of activated Th1 cells and attenuates colitis in Galphai2-deficient mice.

Journal article
Authors Lena Öhman
R Willén
Olof H. Hultgren
Elisabeth Hultgren-Hörnquist
Published in Clinical and experimental immunology
Volume 141
Issue 1
Pages 37-46
ISSN 0009-9104
Publication year 2005
Published at Institute of Laboratory Medicine, Dept of Clinical Immunology
Pages 37-46
Language en
Links dx.doi.org/10.1111/j.1365-2249.2005...
Keywords Adhesins, Bacterial, immunology, Animals, Antigens, Bacterial, immunology, Apoptosis, immunology, Colitis, Ulcerative, immunology, pathology, therapy, Disease Models, Animal, GTP-Binding Protein alpha Subunits, deficiency, Hemagglutinins, immunology, Immunity, Mucosal, Immunoglobulin G, blood, Interleukin-10, biosynthesis, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Pertussis Vaccine, immunology, therapeutic use, Survival Rate, Th1 Cells, immunology, Virulence Factors, Bordetella, immunology
Subject categories Medical and Health Sciences

Abstract

Mice deficient for the inhibitory G protein subunit alpha2 (Galphai2(-/-)) spontaneously develop a progressive inflammatory bowel disease resembling ulcerative colitis, and have a T helper 1 (Th1)-dominated immune response prior to onset of colitis, which is further augmented after the onset of disease. The present study was performed to investigate whether the Galphai2(-/-) mice were able to down-regulate the Th1-dominated inflammatory mucosal immune response and/or induce an anti-inflammatory Th2/T regulatory response and thereby diminish the severity of colitis following treatment with acellular Bordetella pertussis vaccine. The acellular vaccine against B. pertussis, the causative agent of whooping cough, has been demonstrated to induce a Th2-mediated response in both man and mice. We therefore treated Galphai2(-/-) mice intraperitoneally with a three-component acellular B. pertussis vaccine. The treated Galphai2(-/-) mice showed significantly increased interleukin (IL)-10 production in intestinal tissue, associated with significantly reduced colitis and decreased mortality, compared to untreated Galphai2(-/-) mice. The attenuation of colitis in Galphai2(-/-) mice was due, at least partly, to the B. pertussis surface antigen filamentous haemagglutinin (FHA), which almost completely inhibited proliferation of CD4(+) T cells and stimulated apoptosis of activated CD4(+) T helper 1 cells. In conclusion, the three-component acellular B. pertussis vaccine containing filamentous haemagglutinin increases the production of IL-10 in the intestinal mucosa, induces apoptosis of activated Th1 cells and attenuates colitis in Galphai2(-/-) mice.

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