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-γ were also decreased whilst IL-10 and IL-1β 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-1β levels but reduced TLR2+CD14+ monocytes. For pneumococcal WCA-RSV co-stimulation, VitD ₃ only had a limited effect, mainly through increased IL-1β 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.
(Copyright © 2020 Anderson, Do, Toh, Hoe, Reitsma, Mulholland and Licciardi.)