Osteopontin protects against pneumococcal infection in a murine model of allergic airway inflammation.
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.
['Kasetty|Gopinath|G|0000-0001-7552-9708', 'Bhongir|Ravi K V|RKV|0000-0001-6648-1781', 'Papareddy|Praveen|P|', 'Tufvesson|Ellen|E|', 'Stenberg|Henning|H|', 'Bjermer|Leif|L|', 'Hultgårdh-Nilsson|Anna|A|', 'Herwald|Heiko|H|', 'Egesten|Arne|A|']
D000818:Animals D001249:Asthma D058491:Bacterial Load D001992:Bronchoalveolar Lavage Fluid D004195:Disease Models, Animal D006801:Humans D007249:Inflammation D055370:Lung Injury D051379:Mice D018345:Mice, Knockout D053495:Osteopontin D011008:Pneumococcal Infections D020011:Protective Agents D039981:Pyroglyphidae
osteopontin asthma house dust mite Streptococcus pneumoniae allergy host defense