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Protection of Batf3 ‐deficient mice from experimental cerebral malaria correlates with impaired cytotoxic T‐cell responses and immune regulation
Author(s) -
Kuehlwein Janina M.,
Borsche Max,
Korir Patricia J.,
Risch Frederic,
Mueller AnnKristin,
Hübner Marc P.,
Hildner Kai,
Hoerauf Achim,
Dunay Ildiko Rita,
Schumak Beatrix
Publication year - 2020
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13137
Subject(s) - cytotoxic t cell , plasmodium berghei , immune system , cd8 , biology , immunology , granzyme b , antigen presentation , cerebral malaria , t cell , plasmodium falciparum , malaria , in vitro , biochemistry
Summary Excessive inflammatory immune responses during infections with Plasmodium parasites are responsible for severe complications such as cerebral malaria (CM) that can be studied experimentally in mice. Dendritic cells (DCs) activate cytotoxic CD8 + T‐cells and initiate immune responses against the parasites. Batf3 −/− mice lack a DC subset, which efficiently induces strong CD8 T‐cell responses by cross‐presentation of exogenous antigens. Here we show that Batf3 −/− mice infected with Plasmodium berghei ANKA (PbA) were protected from experimental CM (ECM), characterized by a stable blood−brain barrier (BBB) and significantly less infiltrated peripheral immune cells in the brain. Importantly, the absence of ECM in Batf3 −/− mice correlated with attenuated responses of cytotoxic T‐cells, as their parasite‐specific lytic activity as well as the production of interferon gamma and granzyme B were significantly decreased. Remarkably, spleens of ECM‐protected Batf3 −/− mice had elevated levels of regulatory immune cells and interleukin 10. Thus, protection from ECM in PbA‐infected Batf3 −/− mice was associated with the absence of strong CD8 + T‐cell activity and induction of immunoregulatory mediators and cells.