Protection of Batf3-deficient mice from experimental cerebral malaria correlates with impaired cytotoxic T-cell responses and immune regulation

Kuehlwein JM, Borsche M, Korir PJ, Risch F, Mueller AK, Huebner MP, Hildner K, Hoerauf A, Dunay IR, Schumak B (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Immunology Wiley-Blackwell

DOI: 10.1111/imm.13137

Abstract

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.

Authors with CRIS profile

Kai Hildner Professur für Mukosale Immuntherapie

Involved external institutions

Universitätsklinikum Bonn DE Germany (DE) Otto-von-Guericke-Universität Magdeburg DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE)

How to cite

APA:

Kuehlwein, J.M., Borsche, M., Korir, P.J., Risch, F., Mueller, A.-K., Huebner, M.P.,... Schumak, B. (2019). Protection of Batf3-deficient mice from experimental cerebral malaria correlates with impaired cytotoxic T-cell responses and immune regulation. Immunology. https://dx.doi.org/10.1111/imm.13137

MLA:

Kuehlwein, Janina M., et al. "Protection of Batf3-deficient mice from experimental cerebral malaria correlates with impaired cytotoxic T-cell responses and immune regulation." Immunology (2019).

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