Batf3 deficiency proves the pivotal role of CD8α+dendritic cells in protection induced by vaccination with attenuated Plasmodium sporozoites.
Increasing evidence indicates that hepatic CD8α+dendritic cells (DCs) are important antigen cross-presenting cells (APC) involved in the priming of protective CD8+T-cell responses induced by live-attenuated Plasmodium sporozoites. Experimental proof for a critical role of CD8α+DCs in protective pre-erythrocytic malaria immunizations has pivotal implications for vaccine development, including improved vectored subunit vaccines. Employing Batf3-/-mice, which lack functional CD8α+DCs, we demonstrate that deficiency of these particular APCs completely abolishes protection and corresponding signatures of vaccine-induced immunity. We show that in wild-type, but not in Batf3-/-, mice CD8α+DCs accumulate in the liver after immunization with live irradiation-attenuated P. berghei sporozoites. IFN-γ production by Plasmodium antigen-specific CD8+T cells is dependent on functional Batf3. In addition, our results demonstrate that the dysfunctional cDC-CD8+ T-cell axis correlates with MHC class II upregulation on splenic CD8α-DCs. Collectively, these findings underscore the essential role of CD8α+DCs in robust protection induced by experimental live-attenuated malaria vaccines.
Parasitology Unit, Max Planck Institute for Infection Biology, Berlin, Germany.|Depto. de Microbiologia, Immunologia e Parasitologia, UNIFESP, Sao Paolo, Brazil.
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Montagna
Institute of Medical Microbiology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
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Biswas
University Hospital Erlangen, Medical Department 1, Erlangen, Germany.
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Hildner
Parasitology Unit, Max Planck Institute for Infection Biology, Berlin, Germany.|Institute of Biology, Humboldt University, Berlin, Germany.
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Matuschewski
Institute of Medical Microbiology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
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Dunay
CD8α+ dendritic cells; Plasmodium; irradiated sporozoites; malaria protection