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Differentially imprinted innate immunity by mucosal boost vaccination determines antituberculosis immune protective outcomes, independent of T-cell immunity.
- Source :
-
Mucosal immunology [Mucosal Immunol] 2013 May; Vol. 6 (3), pp. 612-25. Date of Electronic Publication: 2012 Nov 07. - Publication Year :
- 2013
-
Abstract
- Homologous and heterologous parenteral prime-mucosal boost immunizations have shown great promise in combating mucosal infections such as tuberculosis and AIDS. However, their immune mechanisms remain poorly defined. In particular, it is still unclear whether T-cell and innate immunity may be independently affected by these immunization modalities and how it impacts immune protective outcome. Using two virus-based tuberculosis vaccines (adenovirus (Ad) and vesicular stomatitis virus (VSV) vectors), we found that while both homologous (Ad/Ad) and heterologous (Ad/VSV) respiratory mucosal boost immunizations elicited similar T-cell responses in the lung, they led to drastically different immune protective outcomes. Compared with Ad-based boosting, VSV-based boosting resulted in poorly enhanced protection against tuberculosis. Such inferior protection was associated with differentially imprinted innate phagocytes, particularly the CD11c(+)CD11b(+/-) cells, in the lung. We identified heightened type 1 interferon (IFN) responses to be the triggering mechanism. Thus, increased IFN-β severely blunted interleukin-12 responses in infected phagocytes, which in turn impaired their nitric oxide production and antimycobacterial activities. Our study reveals that vaccine vectors may differentially imprint innate cells at the mucosal site of immunization, which can impact immune-protective outcome, independent of T-cell immunity, and it is of importance to determine both T-cell and innate cell immunity in vaccine studies.
- Subjects :
- Animals
Cells, Cultured
Female
Immunity, Cellular
Immunity, Innate
Interferon Type I metabolism
Interleukin-12 metabolism
Mice
Mice, Inbred BALB C
Nitric Oxide metabolism
Adenoviridae immunology
Adenoviridae Infections immunology
Genetic Vectors immunology
Phagocytes immunology
Rhabdoviridae Infections immunology
T-Lymphocytes immunology
Tuberculosis Vaccines administration & dosage
Vesiculovirus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1935-3456
- Volume :
- 6
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Mucosal immunology
- Publication Type :
- Academic Journal
- Accession number :
- 23131783
- Full Text :
- https://doi.org/10.1038/mi.2012.103