Vitamin D Induces Differential Effects on Inflammatory Responses During Bacterial and/or Viral Stimulation of Human Peripheral Blood Mononuclear Cells

Streptococcus pneumoniae (pneumococcus) and respiratory syncytial virus (RSV) are the leading causes of respiratory infections amongst children <5 years of age. Co-infection with these pathogens is common during early life and often associated with increased disease severity. Epidemiological studies have shown that low levels of Vitamin D-3 (VitD(3)) are associated with increased susceptibility to respiratory pathogens. However, the role of VitD(3) in the context of pneumococcal and RSV exposure are poorly understood. We found that VitD(3) significantly reduced Th17 cell expression and IL-17A and IL-22 secretion in peripheral blood mononuclear cells (PBMCs) when stimulated with a pneumococcal whole cell antigen (WCA). Levels of IFN-gamma were also decreased whilst IL-10 and IL-1 beta were increased. Effects of VitD(3) on innate responses following RSV stimulation was limited, only reducing IL-6. VitD(3) also reduced the number of TLR2+CD14+ monocytes, whilst increasing TLR7+CD14+ monocytes and TLR4+CD56+ NK cells. In WCA-stimulated PBMCs, VitD(3) increased IL-1 beta levels but reduced TLR2+CD14+ monocytes. For pneumococcal WCA-RSV co-stimulation, VitD(3) only had a limited effect, mainly through increased IL-1 beta and RANTES as well as TLR4+CD56+ NK cells. Our results suggest that VitD(3) can modulate the inflammatory response to pneumococci but has limited effects during viral or bacterial-viral exposure. This is the first study to examine the effects of VitD(3) in the context of pneumococcal-RSV co-stimulation, with important implications on the potential role of VitD(3) in the control of excessive inflammatory responses during pneumococcal and RSV infections.