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Osteopontin protects against pneumococcal infection in a murine model of allergic airway inflammation
Author(s) -
Kasetty Gopinath,
Bhongir Ravi K. V.,
Papareddy Praveen,
Tufvesson Ellen,
Stenberg Henning,
Bjermer Leif,
HultgårdhNilsson Anna,
Herwald Heiko,
Egesten Arne
Publication year - 2019
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13646
Subject(s) - immunology , inflammation , osteopontin , bronchoalveolar lavage , medicine , proinflammatory cytokine , asthma , allergic inflammation , immune system , streptococcus pneumoniae , lung , biology , microbiology and biotechnology , antibiotics
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 −/− ) C57 BL /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.