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

Abstract

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.

Histone Methyltransferase SETDB1 Promotes Immune Evasion in Colorectal Cancer via FOSB-Mediated Downregulation of MicroRNA-22 through BATF3/PD-L1 Pathway

“…Another study also showed the high BATF3 expression in CRC [ 17 ]. More importantly, BATF3 has been suggested to reduce T cell activity and induce immune reaction [ 32 ].…”

Macrophages Mediate Increased CD8 T Cell Inflammation During Weight Loss in Formerly Obese Mice

“…injection of 10 mg/kg xylazin (Rompun R Bayer, Germany) + 100 mg/ml ketamine (Ratiopharm GmbH Germany). Mice were intracardially perfused with 1x PBS for 5 min to remove circulating and non-adhered blood leukocytes from the organs (12).…”

Synergistic Effect of Combined Artesunate and Tetramethylpyrazine in Experimental Cerebral Malaria

“…Protecting the host brain vascular system and neurons and modulating the host inflammatory response to infection might be effective strategies to improve the success of antimalarial therapy for CM . Dysfunction of the brain blood vessels might be the primary cause of CM, preventing the re-establishment of brain homeostasis and leading to treatment failure. , …”

“…4 Dysfunction of the brain blood vessels might be the primary cause of CM, preventing the re-establishment of brain homeostasis and leading to treatment failure. 5,6 Tetramethylpyrazine (TMP) is the primary active alkaloid component of the traditional Chinese medicine Chuanxiong. 7,8 TMP has been demonstrated to increase cerebral blood flow, improve microcirculation, inhibit the production of proinflammatory factors, and protect learning and memory functions.…”