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Enhancement of immune response against Bordetella spp. by disrupting immunomodulation.

Published version
Peer-reviewed

Type

Article

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Authors

Gestal, Monica C 
Howard, Laura K 
Dewan, Kalyan 
Johnson, Hannah M 

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.

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Journal Title

Scientific reports, volume 9, issue 1

Conference Name

Journal ISSN

2045-2322

Volume Title

Publisher

Sponsorship
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (AI116186, AI122753)
NCATS NIH HHS (UL1 TR002378)
U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS) (UL1TR002378)
NIAID NIH HHS (R01 AI122753, R21 AI116186)