Document Type
Article
Publication Date
2019
College/Unit
School of Medicine
Department/Program/Center
Microbiology, Immunology, and Cell Biology
Abstract
Well-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway. The deletion of btrS in B. bronchiseptica did not affect colonization or initial growth in the respiratory tract of mice, its natural host, but did increase activation of the inflammasome pathway, and recruitment of inflammatory cells. The mutant lacking btrS recruited many more B and T cells into the lungs, where they rapidly formed highly organized and distinctive Bronchial Associated Lymphoid Tissue (BALT) not induced by any wild type Bordetella species, and a much more rapid and strong antibody response than observed with any of these species. Immunity induced by the mutant was measurably more robust in all respiratory organs, providing completely sterilizing immunity that protected against challenge infections for many months. Moreover, the mutant induced sterilizing immunity against infection with other classical bordetellae, including B. pertussis and B. parapertussis, something the current vaccines do not provide. These findings reveal profound immunomodulation by bordetellae and demonstrate that by disrupting it much more robust protective immunity can be generated, providing a pathway to greatly improve vaccines and preventive treatments against these important pathogens.
Digital Commons Citation
Gestal, Monica C.; Howard, Laura K.; Dewan, Kalyan; Johnson, Hannah M.; Barbier, Mariette; Bryant, Clare; Soumana, Illiassou Hamidou; Rivera, Israel; Lina, Bodo; Blas-Machado, Uriel; and Harvill, Eric T., "Enhancement of Immune Response Against Bordetella spp. by Disrupting Immunomodulation" (2019). Faculty & Staff Scholarship. 1380.
https://researchrepository.wvu.edu/faculty_publications/1380
Source Citation
Gestal, M. C., Howard, L. K., Dewan, K., Johnson, H. M., Barbier, M., Bryant, C., … Harvill, E. T. (2019). Enhancement of immune response against Bordetella spp. by disrupting immunomodulation. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-56652-z
Included in
Cell Biology Commons, Other Immunology and Infectious Disease Commons, Other Microbiology Commons
Comments
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © Te Author(s) 2019