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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Vitamin D Induces Differential Effects on Inflammatory Responses During Bacterial and/or Viral Stimulation of Human
Jeremy Anderson1, Lien Anh Ha Do1,2, Zheng Quan Toh1,2
1Murdoch Children's Research Institute, Melbourne, VIC, Australia.
Insights
Vitamin D3 (VitD3) modulates inflammatory responses to pneumococcal infections in children, but has limited effects on respiratory syncytial virus (RSV) or co-infections. This research explores VitD3
Area of Science:
- Immunology
- Microbiology
- Nutritional Science
Background:
- Streptococcus pneumoniae (pneumococcus) and respiratory syncytial virus (RSV) are leading causes of respiratory infections in children under 5.
- Co-infections are common and linked to increased disease severity.
- Low Vitamin D3 (VitD3) levels are associated with higher susceptibility to respiratory pathogens, but its role in pneumococcal and RSV co-infection is unclear.
Purpose of the Study:
- To investigate the effects of Vitamin D3 (VitD3) on immune responses to pneumococcal and RSV stimulation, both individually and in co-infection.
- To understand VitD3's role in modulating inflammatory responses in the context of common childhood respiratory infections.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) were stimulated with pneumococcal whole cell antigen (WCA) and/or RSV.
- The effects of VitD3 on cytokine secretion (IL-17A, IL-22, IFN-γ, IL-10, IL-1β, IL-6, RANTES) and monocyte/NK cell populations (TLR expression) were analyzed.
Main Results:
- VitD3 significantly reduced Th17 cell expression and IL-17A/IL-22 secretion in response to pneumococcal WCA.
- VitD3 modulated innate responses to RSV, primarily by reducing IL-6, and altered monocyte and NK cell populations.
- For pneumococcal-RSV co-stimulation, VitD3 had limited effects, mainly increasing IL-1β and RANTES and TLR4+CD56+ NK cells.
Conclusions:
- Vitamin D3 can modulate inflammatory responses to pneumococcal infections.
- VitD3 demonstrates limited efficacy in modulating immune responses during viral (RSV) or bacterial-viral co-exposure.
- This study provides novel insights into the potential role of VitD3 in managing excessive inflammation during pneumococcal and RSV infections.
Abstract:
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 D3 (VitD3) are associated with increased susceptibility to respiratory pathogens. However, the role of VitD3 in the context of pneumococcal and RSV exposure are poorly understood. We found that VitD3 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 VitD3 on innate responses following RSV stimulation was limited, only reducing IL-6. VitD3 also reduced the number of TLR2+CD14+ monocytes, whilst increasing TLR7+CD14+ monocytes and TLR4+CD56+ NK cells. In WCA-stimulated PBMCs, VitD3 increased IL-1β levels but reduced TLR2+CD14+ monocytes. For pneumococcal WCA-RSV co-stimulation, VitD3 only had a limited effect, mainly through increased IL-1β and RANTES as well as TLR4+CD56+ NK cells. Our results suggest that VitD3 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 VitD3 in the context of pneumococcal-RSV co-stimulation, with important implications on the potential role of VitD3 in the control of excessive inflammatory responses during pneumococcal and RSV infections.
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