C-type lectin receptors (CLRs) are important pattern recognition receptors involved in recognition and induction of adaptive immunity to pathogens. Certain CLRs play an important role in viral infections as they efficiently interact with viruses. However, it has become clear that deadly viruses subvert the function of CLRs to escape antiviral immunity and promote infection. In particular, viruses target CLRs to suppress or modulate type I interferons that play a central role in the innate and adaptive defense against viruses. In this review, we discuss the function of CLRs in binding to enveloped viruses like HIV-1 and Dengue virus, and how uptake and signaling cascades have decisive effects on the outcome of infection.

A hallmark of HIV-1 infection is the lack of sterilizing immunity. Dendritic cells (DCs) are crucial in the induction of immunity, and lack of DC activation might underlie the absence of an effective anti–HIV-1 response. We have investigated how HIV-1 infection affects maturation of DCs. Our data show that even though DCs are productively infected by HIV-1, infection does not induce DC maturation. HIV-1 infection actively suppresses DC maturation, as HIV-1 infection inhibited TLR-induced maturation of DCs and thereby decreased the immune stimulatory capacity of DCs. Interfering with SAMHD1 restriction further increased infection of DCs, but did not lead to DC maturation. Notably, higher infection observed with SAMHD1 depletion correlated with a stronger suppression of maturation. Furthermore, blocking reverse transcription rescued TLR-induced maturation. These data strongly indicate that HIV-1 replication does not trigger immune activation in DCs, but that HIV-1 escapes immune surveillance by actively suppressing DC maturation independent of SAMHD1. Elucidation of the mechanism of suppression can lead to promising targets for therapy or vaccine design.

While vaccine-induced SARS-CoV-2 antibodies provide partial protection against COVID-19, a significant question remains regarding the role of vaccine-induced T cells in combating COVID-19. The purpose of this study is to investigate whether signatures of the T-cell response contribute to protection against (severe) COVID-19. T cell receptor (TCR) sequencing was conducted using pre-vaccination and 29 days post-vaccination PAXgene samples from 396 participants in the phase 3 efficacy trial, ENSEMBLE. The dataset consists of 198 individuals who developed breakthrough COVID-19 infections, including 23 severe cases, and an equal number of matched control subjects. Immunosequencing and subsequent computational analysis was performed to identify SARS-CoV-2 and Spike-specific TCRs to quantify SARS-CoV-2 specific T cell breadth, depth, clonal expansion, and a model test score that describes magnitude of cellular response compared to pre-pandemic controls. Preliminary analyses demonstrated high concordance and correlation between functional T cell responses measured by a standard intracellular cytokine staining and TCR sequencing metrics. Furthermore, vaccine-elicited T cell responses correlated inversely with the risk of developing severe COVID-19, while no strong relation was observed with overall symptomatic COVID-19 risk. A multivariable analysis including neutralizing antibody data and TCR scores indicated that, in addition to humoural responses, T cell responses contribute to protection against severe COVID-19. Our findings show that higher vaccine-elicited T cell responses are significantly correlated with decreased risk of severe COVID-19, but not with risk of any symptomatic COVID-19. These results represent a direct correlation between vaccine-elicited T cell responses and protection from severe COVID-19. This work was fully funded by Janssen Vaccines & Prevention B.V. The samples were sourced from ENSEMBLE, which was partly funded by Biomedical Advanced Research and Development Authority (BARDA), under other transaction agreement HHSO100201700018C.

Plasmodium sexual stages represent a critical bottleneck in the parasite life cycle. Gametocytes taken up in an infectious blood meal by female anopheline mosquito get activated to form gametes and fuse to form short-lived zygotes, which transform into ookinetes to infect mosquitoes.

Innate sensing of HIV-1 by dendritic cells (DCs) initiates cell-intrinsic signalling programs that direct virus restriction and antiviral defenses. These responses include the production of type I interferon (IFN) and a large number of IFN-stimulated genes (ISGs) with a broad spectrum of antiviral effector functions. Initial interactions of HIV-1 at the mucosal surfaces with DC-expressed innate immune factors including cGAS, TRIM5α and SAMHD1 are predictive of viraemia, inflammation and disease pathogenesis. Here, we review the molecular basis of HIV-1 sensing in the two major mucosal DC subsets, that is, epithelial Langerhans cells and subepithelial CD11c+ conventional DCs. We discuss the concerted actions of the host restriction factors and innate sensors as well as viral evasion mechanisms in determining HIV-1 susceptibility to infection and directing antiviral adaptive immune response