Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity

McKee, A.S., Munks, M.W., MacLeod, M.K.L. , Fleenor, C.J., Van Rooijen, N., Kappler, J.W. and Marrack, P. (2009) Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity. Journal of Immunology, 183(7), pp. 4403-4414. (doi: 10.4049/jimmunol.0900164)

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Publisher's URL: http://dx.doi.org/10.4049/jimmunol.0900164

Abstract

To understand more about how the body recognizes alum we characterized the early innate and adaptive responses in mice injected with the adjuvant. Within hours of exposure, alum induces a type 2 innate response characterized by an influx of eosinophils, monocytes, neutrophils, DCs, NK cells and NKT cells. In addition, at least 13 cytokines and chemokines are produced within 4 h of injection including IL-1β and IL-5. Optimal production of some of these, including IL-1β, depends upon both macrophages and mast cells, whereas production of others, such as IL-5, depends on mast cells only, suggesting that both of these cell types can detect alum. Alum induces eosinophil accumulation partly through the production of mast cell derived IL-5 and histamine. Alum greatly enhances priming of endogenous CD4 and CD8 T cells independently of mast cells, macrophages, and of eosinophils. In addition, Ab levels and Th2 bias was similar in the absence of these cells. We found that the inflammation induced by alum was unchanged in caspase-1-deficient mice, which cannot produce IL-1β. Furthermore, endogenous CD4 and CD8 T cell responses, Ab responses and the Th2 bias were also not impacted by the absence of caspase-1 or NLRP3. These data suggest that activation of the inflammasome and the type 2 innate response orchestrated by macrophages and mast cells in vivo are not required for adjuvant effect of alum on endogenous T and B cell responses.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Macleod, Dr Megan
Authors: McKee, A.S., Munks, M.W., MacLeod, M.K.L., Fleenor, C.J., Van Rooijen, N., Kappler, J.W., and Marrack, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Immunology
Journal Abbr.:J. Immunol.
ISSN:0022-1767
ISSN (Online):1550-6606
Published Online:04 September 2009

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