Cd14 SNPs regulate the innate immune response

CD14 is a monocytic differentiation antigen that regulates innate immune responses to pathogens. Here, we show that murine Cd14 SNPs regulate the length of Cd14 mRNA and CD14 protein translation efficiency, and consequently the basal level of soluble CD14 (sCD14) and type I IFN production by murine macrophages. This has substantial downstream consequences for the innate immune response; the level of expression of at least 40 IFN-responsive murine genes was altered by this mechanism. We also observed that there was substantial variation in the length of human CD14 mRNAs and in their translation efficiency. sCD14 increased cytokine production by human dendritic cells (DCs), and sCD14-primed DCs augmented human CD4T cell proliferation. These findings may provide a mechanism for exploring the complex relationship between CD14 SNPs, serum sCD14 levels, and susceptibility to human infectious and allergic diseases.

► We discovered a novel genetic mechanism affecting murine CD14 translation and secretion.
► Variation in human CD14 transcript length also affects its translational efficiency.
► Soluble CD14 altered human dendritic cell cytokine production and augmented T cell responses.
► This data provide a novel context for evaluating the role of CD14 in human disease susceptibility.