Osteopontin protects against pneumococcal infection in a murine model of allergic airway inflammation. Issue 4 (19th November 2018)

• Record Type: Journal Article
• Authors: Kasetty, Gopinath; Bhongir, Ravi K. V.; Papareddy, Praveen; Tufvesson, Ellen; Stenberg, Henning; Bjermer, Leif; Hultgårdh‐Nilsson, Anna; Herwald, Heiko; Egesten, Arne
• Is Part Of: Allergy. Volume 74:Issue 4(2019)
• Page Start: 663
• Page End: 674
• Publication Date: 2018-11-19
• Subjects: allergy -- asthma -- host defense -- house dust mite -- osteopontin -- Streptococcus pneumoniae; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.13646
• Languages: English
• ISSNs: 0105-4538

Abstract

Abstract: Background: In atopic asthma, chronic Th2‐biased inflammation is associated with an increased risk of pneumococcal infection. The anionic phosphoglycoprotein osteopontin (OPN) is highly expressed in asthma and has been ascribed several roles during inflammation. This study aimed to investigate whether OPN affects inflammation and vulnerability to pneumococcal infection in atopic asthma. Methods: House dust mite (HDM) extract was used to induce allergic airway inflammation in both wild‐type ( Spp1 +/+ ) and OPN knockout ( Spp1 −/− ) C57BL/6J mice, and the airway was then infected with Streptococcus pneumoniae . Parameters reflecting inflammation, tissue injury, and bacterial burden were measured. In addition, samples from humans with allergic asthma were analyzed. Results: Both allergen challenge in individuals with allergic asthma and the intranasal instillation of HDM in mice resulted in increased OPN levels in bronchoalveolar lavage fluid (BALF). More immune cells (including alveolar macrophages, neutrophils, eosinophils, and lymphocytes) and higher levels of proinflammatory cytokines were found in Spp1 −/− mice than in Spp1 +/+ mice. Moreover, OPN‐deficient mice exhibited increased levels of markers reflecting tissue injury. Upon infection with S . pneumoniae, Spp1 +/+ mice with allergic airway inflammation had a significantly lower bacterial burden in both BALF and lung tissue than did Spp1 −/− mice. Furthermore, Spp1 −/− mice had higher levels of cytokines and immune cells in BALF than did Spp1 +/+ mice. Conclusion: OPN reduces inflammation, decreases tissue injury, and reduces bacterial loads during concurrent pneumococcal infection and allergic airway inflammation in a murine model. These findings suggest that OPN significantly affects vulnerability to pneumococcal infection in atopic asthma. Abstract : HDM‐instillation to the airways causes increased inflammation and tissue damage in osteopontin‐deficient mice. Osteopontin‐deficient mice ( Spp1 ‐/‐ ) with an ongoing allergic airway inflammation are more prone to pneumococcal infection. The findings suggest that osteopontin plays important roles, modulating inflammation, tissue damage, and host defense against pneumococcal infection during allergic asthma.