The role of UV radiation and vitamin D in the seasonality and outcomes of infectious disease

The seasonality of infectious disease outbreaks suggests that environmental conditions have a significant effect on disease risk. One of the major environmental factors that can affect this is solar radiation, primarily acting through ultraviolet radiation (UVR), and its subsequent control of vitamin D production. Here we show how UVR and vitamin D, which are modified by latitude and season, can affect host and pathogen fitness and relate them to the outcomes of bacterial, viral and vector-borne infections. We conducted a thorough comparison of the molecular and cellular mechanisms of action of UVR and vitamin D on pathogen fitness and host immunity and related these to the effects observed in animal models and clinical trials to understand their independent and complementary effects on infectious disease outcome. UVR and vitamin D share common pathways of innate immune activation primarily via antimicrobial peptide production, and adaptive immune suppression. Whilst UVR can induce vitamin D-independent effects in the skin, such as the generation of photoproducts activating interferon signaling, vitamin D has a larger systemic effect due to its autocrine and paracrine modulation of cellular responses in a range of tissues. However, the seasonal patterns in infectious disease prevalence are not solely driven by variation in UVR and vitamin D levels across latitudes. Vector-borne pathogens show a strong seasonality of infection correlated to climatic conditions favoring their replication. Conversely, pathogens, such as influenza A virus, Mycobacterium tuberculosis and human immunodeficiency virus type 1, have strong evidence to support their interaction with vitamin D. Thus, UVR has both vitamin D-dependent and independent effects on infectious diseases; these effects vary depending on the pathogen of interest and the effects can be complementary or antagonistic.