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NK cells influence both innate and adaptive immune responses after mucosal immunization with antigen and mucosal adjuvant.

ABSTRACT: NK cells were found to be recruited in a temporally controlled manner to the nasal-associated lymphoid tissue and the cervical lymph nodes of mice after intranasal immunization with Ag85B-early secreted antigenic target 6 kDa from Mycobacterium tuberculosis mixed with Escherichia coli heat-labile toxin as adjuvant. These NK cells were activated and secreted a diverse range of cytokines and other immunomodulators. Using Ab depletion targeting anti-asialo GM1, we found evidence for altered trafficking, impaired activation, and cytokine secretion of dendritic cells, macrophages, and neutrophils in immunized NK cell-depleted mice compared with control animals. Analysis of Ag-specific immune responses revealed an attenuated Ab and cytokine response in immunized NK cell-depleted animals. Systemic administration of rIL-6 but not rIFN-gamma significantly restored immune responses in mice depleted of NK cells. In conclusion, cytokine production, particularly IL-6, via NK cells and NK cell-activated immune populations plays an important role in the establishment of local innate immune responses and the consequent development of adaptive immunity after mucosal immunization.

SUBMITTER: Hall LJ

PROVIDER: S-EPMC3517975 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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NK cells influence both innate and adaptive immune responses after mucosal immunization with antigen and mucosal adjuvant.

Hall Lindsay J LJ Clare Simon S Dougan Gordon G

Journal of immunology (Baltimore, Md. : 1950) 20100310 8

NK cells were found to be recruited in a temporally controlled manner to the nasal-associated lymphoid tissue and the cervical lymph nodes of mice after intranasal immunization with Ag85B-early secreted antigenic target 6 kDa from Mycobacterium tuberculosis mixed with Escherichia coli heat-labile toxin as adjuvant. These NK cells were activated and secreted a diverse range of cytokines and other immunomodulators. Using Ab depletion targeting anti-asialo GM1, we found evidence for altered traffic ...[more]

PMID: 20220095

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Project description:Infectious bronchitis (IB) caused by infectious bronchitis virus (IBV) is currently a major threat to chicken health, with multiple outbreaks being reported in the United States over the past decade. Modified live virus (MLV) vaccines used in the field can persist and provide the genetic material needed for recombination and emergence of novel IBV serotypes. Inactivated and subunit vaccines overcome some of the limitations of MLV with no risk of virulence reversion and emergence of new virulent serotypes. However, these vaccines are weakly immunogenic and poorly protective. There is an urgent need to develop more effective vaccines that can elicit a robust, long-lasting immune response. In this study, we evaluate a novel adjuvant system developed from Quil-A and chitosan (QAC) for the intranasal delivery of nucleic acid immunogens to improve protective efficacy. The QAC adjuvant system forms nanocarriers (<100 nm) that efficiently encapsulate nucleic acid cargo, exhibit sustained release of payload, and can stably transfect cells. Encapsulation of plasmid DNA vaccine expressing IBV nucleocapsid (N) protein by the QAC adjuvant system (pQAC-N) enhanced immunogenicity, as evidenced by robust induction of adaptive humoral and cellular immune responses postvaccination and postchallenge. Birds immunized with pQAC-N showed reduced clinical severity and viral shedding postchallenge on par with protection observed with current commercial vaccines without the associated safety concerns. Presented results indicate that the QAC adjuvant system can offer a safer alternative to the use of live vaccines against avian and other emerging coronaviruses.IMPORTANCE According to 2017 U.S. agriculture statistics, the combined value of production and sales from broilers, eggs, turkeys, and chicks was $42.8 billion. Of this number, broiler sales comprised 67% of the industry value, with the production of >50 billion pounds of chicken meat. The economic success of the poultry industry in the United States hinges on the extensive use of vaccines to control infectious bronchitis virus (IBV) and other poultry pathogens. The majority of vaccines currently licensed for poultry health include both modified live vaccine and inactivated pathogens. Despite their proven efficacy, modified live vaccine constructs take time to produce and could revert to virulence, which limits their safety. The significance of our research stems from the development of a safer and potent alternative mucosal vaccine to replace live vaccines against IBV and other emerging coronaviruses.

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NK cells influence both innate and adaptive immune responses after mucosal immunization with antigen and mucosal adjuvant.

Publications

NK cells influence both innate and adaptive immune responses after mucosal immunization with antigen and mucosal adjuvant.

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