Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection |
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Authors: | Jonathan K. Nambiar Anthony A. Ryan Carlyn U. Kong Warwick J. Britton James A. Triccas |
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Affiliation: | 1. Microbial Pathogenesis and Immunity Group, Discipline of Infectious Diseases and Immunology, University of Sydney, NSW, Australia;2. Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney, NSW, Australia;3. Discipline of Medicine, University of Sydney, NSW, Australia |
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Abstract: | The rational design of new vaccines engineered to target key components of the host immune response is crucial to aid control of important infectious diseases such as tuberculosis. In this report, we determined whether modifying the function of pulmonary APC could improve protection against infection with Mycobacterium tuberculosis. Targeted delivery to the lung of the cytokine GM‐CSF, expressed by the Mycobacterium bovis BCG vaccine strain, increased pulmonary DC numbers and secretion of the immunoregulatory cytokine IL‐12, compared with parental BCG immunization. This impact on APC number by BCG:GM‐CSF resulted in accelerated priming of antigen‐specific CD4+ T cells in the mediastinal lymph nodes and increased migration of activated CD4+ T cells into the lung. i.n. administration of BCG:GM‐CSF resulted in significantly increased protection against M. tuberculosis infection compared with mice vaccinated with BCG alone. BCG:GM‐CSF exhibited an improved safety profile, as immunodeficient RAG1?/? mice vaccinated i.n. with BCG:GM‐CSF survived significantly longer than control BCG‐vaccinated mice. These data demonstrate that manipulating immune cells in the lung by BCG‐based delivery of GM‐CSF can assist the development of protective mucosal immunity against pulmonary bacterial infection. |
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Keywords: | APC Cytokine Infectious disease Vaccination |
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