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Batf3 deficiency proves the pivotal role of CD 8α + dendritic cells in protection induced by vaccination with attenuated Plasmodium sporozoites
Author(s) -
Montagna G. N.,
Biswas A.,
Hildner K.,
Matuschewski K.,
Dunay I. R.
Publication year - 2015
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/pim.12222
Subject(s) - plasmodium berghei , biology , immunology , antigen , cross presentation , cd8 , vaccination , priming (agriculture) , virology , immune system , malaria , dendritic cell , immunity , plasmodium (life cycle) , immunization , major histocompatibility complex , mhc class i , parasite hosting , world wide web , computer science , botany , germination
Summary Increasing evidence indicates that hepatic CD 8α + dendritic cells ( DC s) are important antigen cross‐presenting cells ( APC ) involved in the priming of protective CD 8 + T‐cell responses induced by live‐attenuated Plasmodium sporozoites. Experimental proof for a critical role of CD 8α + DC s in protective pre‐erythrocytic malaria immunizations has pivotal implications for vaccine development, including improved vectored subunit vaccines. Employing Batf3 −/− mice, which lack functional CD 8α + DC s, we demonstrate that deficiency of these particular APC s completely abolishes protection and corresponding signatures of vaccine‐induced immunity. We show that in wild‐type, but not in Batf3 −/− , mice CD 8α + DC s accumulate in the liver after immunization with live irradiation‐attenuated P. berghei sporozoites. IFN ‐γ production by Plasmodium antigen‐specific CD 8 + T cells is dependent on functional Batf3. In addition, our results demonstrate that the dysfunctional cDC ‐ CD 8+ T‐cell axis correlates with MHC class II upregulation on splenic CD 8α − DC s. Collectively, these findings underscore the essential role of CD 8α + DC s in robust protection induced by experimental live‐attenuated malaria vaccines.