Abstract
The Type Six Secretion System (T6SS) is required for Bordetella bronchiseptica cytotoxicity, cytokine modulation, infection, and persistence. However, one-third of recently sequenced Bordetella bronchiseptica strains of the predominantly human-associated Complex IV have lost their T6SS through gene deletion or degradation. Since most human B. bronchiseptica infections occur in immunocompromised patients, we determine here whether loss of Type Six Secretion is beneficial to B. bronchiseptica during infection of immunocompromised mice. Infection of mice lacking adaptive immunity (Rag1-/- mice) with a T6SS-deficient mutant results in a hypervirulent phenotype that is characterized by high numbers of intracellular bacteria in systemic organs. In contrast, wild-type B. bronchiseptica kill their eukaryotic cellular hosts via a T6SS-dependent mechanism that prevents survival in systemic organs. High numbers of intracellular bacteria recovered from immunodeficient mice but only low numbers from wild-type mice demonstrates that B. bronchiseptica survival in an intracellular niche is limited by B and T cell responses. Understanding the nature of intracellular survival during infection, and its effects on the generation and function of the host immune response, are important to contain and control the spread of Bordetella-caused disease.
Highlights
The ability of bacteria to persist inside host cells shields them from antibodies, complement, and other-extracellular host defenses and represents an effective strategy for survival during infection
The B. bronchiseptica T6SS is required for persistence during infection of wild-type mice [29], we show that loss of this secretion system contributes to enhanced intracellular survival leading to early host death of immunodeficient mice
Disruption of T6SS function is detrimental for B. bronchiseptica in adaptive immunodeficient mice; while high numbers of RB50ΔclpV survived intracellularly at the site of infection, the spread of mutant to systemic organs via long-term survival in Antigen Presenting Cells (APCs) contributed to host death, representing a “dead-end” for B. bronchiseptica (Figs 6 and 2)
Summary
The ability of bacteria to persist inside host cells shields them from antibodies, complement, and other-extracellular host defenses and represents an effective strategy for survival during infection. Bordetella species were generally considered exclusively extracellular respiratory pathogens [4], but in vitro studies suggest that the Bordetella may be able to survive intracellularly [5,6,7,8,9,10,11,12]. The three Classical Bordetellae, Bordetella bronchiseptica, B. pertussis, and B. parapertussis, cause a variety of respiratory diseases ranging from asymptomatic infection to fatal pneumonia [13]. There have been reports of the recovery of B. pertussis and B. bronchiseptica from bronchiolar lavage of mice, murine nasal cavity dendritic cells, and alveolar macrophages from HIV-infected patients [19,20,21], suggesting that intracellular survival is a potential mechanism employed by B. bronchiseptica during infection. Defining the role of intracellular survival in Bordetella disease has important implications for the development of vaccines and therapeutics
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
