Description: Cerebral malaria (CM) is the most severe complication of malaria. The murine Plasmodium berghei ANKA (PbA) infection model has helped to identify crucial players in the pathogenesis of CM. However, the role of pattern recognition receptors in innate immunity to CM induction is still poorly understood. C-type lectin receptors (CLRs) represent a family of pattern recognition receptors that recognize carbohydrate structures on pathogens and self-Ags often in a Ca 2+ -dependent manner. In this study, we investigated the role of the CLR dendritic cell immunoreceptor (DCIR) in the genesis of CM. Using the murine PbA infection, we show in this article that DCIR is essential for the development of CM. Although PbA infection led to 80% CM in wild-type C57BL/6 mice, DCIR-deficient mice were highly protected with only 15% CM development. In accordance with the reduced CM incidence in DCIR –/– mice, CD8 + T cell sequestration was markedly reduced in brains of PbA-infected DCIR –/– mice, which was accompanied by reduced brain inflammation. Reduced T cell sequestration in the brain was caused by decreased TNF-α levels in sera, as well as a modulated activation of CD4 + and CD8 + T cells in spleen of PbA-infected DCIR –/– mice. This study indicates that DCIR is critically involved in CM induction, thus highlighting the importance of this CLR in innate immunity during malaria infection.

Description: The glycoproteins hemagglutinin (HA) and neuraminidase are the major determinants of host range and tissue tropism of the influenza virus. HA is the most abundant protein in the virus particle membrane and represents the basis of most influenza vaccines. It has been reported that influenza virus HA N -glycosylation markedly depends on the host cell line used for virus production. However, little is known about how differential glycosylation affects immunogenicity of the viral proteins. This is of importance for virus propagation in chicken eggs as well as for innovative influenza vaccine production in mammalian cell lines. In this study, we investigated the impact of the differential N -glycosylation patterns of two influenza A virus PR/8/34 (H1N1) variants on immunogenicity. Madin–Darby canine kidney cell–derived and Vero cell–derived glycovariants were analyzed for immunogenicity in a TCR-HA transgenic mouse model. Next-generation pyrosequencing validated the congruence of the potential HA N -glycosylation sites as well as the presence of the HA peptide recognized by the TCR-HA transgenic T cells. We show that differential HA N -glycosylation markedly affected T cell activation and cytokine production in vitro and moderately influenced IL-2 production in vivo. Cocultivation assays indicated that the difference in immunogenicity was mediated by CD11c + dendritic cells. Native virus deglycosylation by endo- and exoglycosidases dramatically reduced cytokine production by splenocytes in vitro and markedly decreased HA-specific Ab production in vivo. In conclusion, this study indicates a crucial importance of HA N -glycosylation for immunogenicity. Our findings have implications for cell line–based influenza vaccine design.