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In mice, the IgG subclass induced after Ag encounter can reflect the nature of the Ag. Th2 Ags such as alum-precipitated proteins and helminths induce IgG1, whereas Th1 Ags, such as Salmonella Typhimurium, predominantly induce IgG2a. The contribution of different IgG isotypes to protection against bacteria such as S. Typhimurium is unclear, although as IgG2a is induced by natural infection, it is assumed this isotype is important. Previously, we have shown that purified S. Typhimurium porins including outer membrane protein OmpD, which induce both IgG1 and IgG2a in mice, provide protection to S. Typhimurium infection via Ab. In this study we report the unexpected finding that mice lacking IgG1, but not IgG2a, are substantially less protected after porin immunization than wild-type controls. IgG1-deficient mice produce more porin-specific IgG2a, resulting in total IgG levels that are similar to wild-type mice. The decreased protection in IgG1-deficient mice correlates with less efficient bacterial opsonization and uptake by macrophages, and this reflects the low binding of outer membrane protein OmpD-specific IgG2a to the bacterial surface. Thus, the Th2-associated isotype IgG1 can play a role in protection against Th1-associated organisms such as S. Typhimurium. Therefore, individual IgG subclasses to a single Ag can provide different levels of protection and the IgG isotype induced may need to be a consideration when designing vaccines and immunization strategies.

Original publication

DOI

10.4049/jimmunol.1700952

Type

Journal article

Journal

Journal of immunology (baltimore, md. : 1950)

Publication Date

12/2017

Volume

199

Pages

4103 - 4109

Addresses

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom.

Keywords

Cell Line, Animals, Mice, Inbred C57BL, Salmonella typhimurium, Salmonella Infections, Animal, IgG Deficiency, Bacterial Proteins, Porins, Immunoglobulin G, Salmonella Vaccines, Antibodies, Bacterial, Immunoglobulin Isotypes, Immunization, Bacterial Adhesion, Phagocytosis, Antigen-Antibody Reactions, Immunoglobulin Class Switching, Female, Male