High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases.

Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death.

GPR41 and GPR43 regulate CD8 T cell priming during herpes simplex virus type 1 infection.

Naïve CD8 T cells need to undergo a complex and coordinated differentiation program to gain the capacity to control virus infections. This not only involves the acquisition of effector functions, but also regulates the development of a subset of effector CD8 T cells into long-lived and protective memory cells. Microbiota-derived metabolites have recently gained interest for their influence on T cells, but much remains unclear about their role in CD8 T cell differentiation.

CD4 T cell immunity against cutaneous melanoma encompasses multifaceted MHC II-dependent responses.

Whereas CD4 T cells conventionally mediate antitumor immunity by providing help to CD8 T cells, recent clinical studies have implied an important role for cytotoxic CD4 T cells in cancer immunity. Using an orthotopic melanoma model, we provide a detailed account of antitumoral CD4 T cell responses and their regulation by major histocompatibility complex class II (MHC II) in the skin. Intravital imaging revealed prominent interactions of CD4 T cells with tumor debris-laden MHC II host antigen-presenting cells that accumulated around tumor cell nests, although direct recognition of MHC II melanoma cells alone could also promote CD4 T cell control.

Functional flexibility and plasticity in immune control of systemic Salmonella infection.

Immunity to systemic Salmonella infection depends on multiple effector mechanisms. Lymphocyte-derived interferon gamma (IFN-γ) enhances cell-intrinsic bactericidal capabilities to antagonize the hijacking of phagocytes as replicative niches for Salmonella. Programmed cell death (PCD) provides another means through which phagocytes fight against intracellular Salmonella.

CD4 T cell calibration of antigen-presenting cells optimizes antiviral CD8 T cell immunity.

Antiviral CD8 T cell immunity depends on the integration of various contextual cues, but how antigen-presenting cells (APCs) consolidate these signals for decoding by T cells remains unclear. Here, we describe gradual interferon-α/interferon-β (IFNα/β)-induced transcriptional adaptations that endow APCs with the capacity to rapidly activate the transcriptional regulators p65, IRF1 and FOS after CD4 T cell-mediated CD40 stimulation. While these responses operate through broadly used signaling components, they induce a unique set of co-stimulatory molecules and soluble mediators that cannot be elicited by IFNα/β or CD40 alone.