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Parasite Immunol. 2015 Oct;37(10):533-543. doi: 10.1111/pim.12222.

Batf3 deficiency proves the pivotal role of CD8α+ dendritic cells in protection induced by vaccination with attenuated Plasmodium sporozoites.

Author information

1
Parasitology Unit, Max Planck Institute for Infection Biology, Berlin, Germany.
2
Depto. de Microbiologia, Immunologia e Parasitologia, UNIFESP, Sao Paolo, Brazil.
3
Institute of Medical Microbiology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
4
University Hospital Erlangen, Medical Department 1, Erlangen, Germany.
5
Institute of Biology, Humboldt University, Berlin, Germany.

Abstract

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.

KEYWORDS:

CD8α+ dendritic cells; Plasmodium; irradiated sporozoites; malaria protection

PMID:
26284735
DOI:
10.1111/pim.12222
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