Effects of repeated infections with non-typeable Haemophilus influenzae on lung in vitamin D deficient and smoking
Jef Serré1, Ajime Tom Tanjeko1, Carolien Mathyssen1
1Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Herestraat 49, O&NI bis, box 706, 3000, Leuven, Belgium.
Background:
In chronic obstructive pulmonary disease (COPD), exacerbations cause acute inflammatory flare-ups and increase the risk for hospitalization and mortality. Exacerbations are common in all disease stages and are often caused by bacterial infections e.g., non-typeable Heamophilus influenzae (NTHi). Accumulating evidence also associates vitamin D deficiency with the severity of COPD and exacerbation frequency. However, it is still unclear whether vitamin D deficiency when combined with cigarette smoking would worsen and prolong exacerbations caused by repeated infections with the same bacterial strain.
Methods:
Vitamin D sufficient (VDS) and deficient (VDD) mice were exposed to nose-only cigarette smoke (CS) for 14 weeks and oropharyngeally instilled with NTHi at week 6, 10 and 14. Three days after the last instillation, mice were assessed for lung function, tissue remodeling, inflammation and immunity. The impact of VDD and CS on inflammatory cells and immunoglobulin (Ig) production was also assessed in non-infected animals while serum Ig production against NTHi and dsDNA was measured in COPD patients before and 1 year after supplementation with Vitamin D3.
Results:
VDD enhanced NTHi eradication, independently of CS and complete eradication was reflected by decreased anti-NTHi Ig's within the lung. In addition, VDD led to an increase in total lung capacity (TLC), lung compliance (Cchord), MMP12/TIMP1 ratio with a rise in serum Ig titers and anti-dsDNA Ig's. Interestingly, in non-infected animals, VDD exacerbated the CS-induced anti-NTHi Ig's, anti-dsDNA Ig's and inflammatory cells within the lung. In COPD patients, serum Ig production was not affected by vitamin D status but anti-NTHi IgG increased after vitamin D3 supplementation in patients who were Vitamin D insufficient before treatment.
Conclusion:
During repeated infections, VDD facilitated NTHi eradication and resolution of local lung inflammation through production of anti-NTHi Ig, independently of CS whilst it also promoted autoantibodies. In COPD patients, vitamin D supplementation could be protective against NTHi infections in vitamin D insufficient patients. Future research is needed to decipher the determinants of dual effects of VDD on adaptive immunity.
Trail Registration:
ClinicalTrials, NCT00666367. Registered 23 April 2008, https://www.clinicaltrials.gov/ct2/show/study/NCT00666367 .
Insights
Vitamin D deficiency aids bacterial eradication in COPD models, independent of smoking. Vitamin D supplementation may protect insufficient COPD patients from infections.
Area of Science:
- Pulmonary Medicine
- Immunology
- Nutritional Science
Background:
- Chronic obstructive pulmonary disease (COPD) exacerbations are linked to bacterial infections and vitamin D deficiency.
- The combined impact of vitamin D deficiency and smoking on COPD exacerbations remains unclear.
Purpose of the Study:
- To investigate how vitamin D deficiency affects exacerbations caused by non-typeable Heamophilus influenzae (NTHi) in a COPD model involving cigarette smoke.
- To assess the effects of vitamin D supplementation in COPD patients.
Main Methods:
- Mice with sufficient or deficient vitamin D were exposed to cigarette smoke and infected with NTHi.
- Lung function, inflammation, and immune responses were analyzed.
- COPD patients' immunoglobulin (Ig) levels were measured before and after vitamin D3 supplementation.
Main Results:
- Vitamin D deficiency enhanced NTHi eradication and reduced lung inflammation, independent of cigarette smoke.
- Vitamin D deficiency increased lung capacity, compliance, and autoantibodies.
- In COPD patients, vitamin D supplementation increased anti-NTHi IgG in previously deficient individuals.
Conclusions:
- Vitamin D deficiency promotes bacterial clearance and resolves lung inflammation during repeated infections, potentially via Ig production, independent of smoking.
- Vitamin D supplementation may offer protection against NTHi in vitamin D-insufficient COPD patients.
- Further research is needed to understand the complex effects of vitamin D deficiency on adaptive immunity.
