Osteopontin protects against pneumococcal infection in a murine model of allergic airway inflammation

Abstract

BackgroundIn 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.MethodsHouse 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.ResultsBoth 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.ConclusionOPN 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.

Osteopontin as a Link between Inflammation and Cancer: The Thorax in the Spotlight

“…Its absence fails to maintain normal NK cellularity and its stimulation by IL-15 increases cell death [75]. However, OPN limits inflammation, tissue injury, and bacterial load during concurrent pneumococcal infection and allergic airway inflammation [76]. It can be upregulated together with leptin, and both of them may regulate apoptosis, adhesion, migration, and activation of eosinophils, in a PI3K and anti-α4 activation manner [77].…”

“…OPN binds eosinophil-recruiting chemokines inhibiting their antibacterial activity against Streptococcus pneumoniae in parallel with sustained allergic inflammation during asthma [76].…”

Osteopontin Expression in Small Airway Epithelium in Copd is Dependent on Differentiation and Confined to Subsets of Cells

“…Furthermore, OPN is thought to impair host defenses against pneumococcal airway infection in mice and humans, and CS increases the risk of severe pneumococcal disease, further associating OPN to airway infection 38,41 . In contrast, OPN protected against pneumococcal infection in a model of allergic asthma 42 . Its beneficial role was also demonstrated in a model of histone-induced acute lung injury 43 .…”

Identification of transcriptomic characteristics during nasal capsular contracture progression using RNA deep sequencing

“…In addition, SPP1 has also been found to upregulates expression of interferon-gamma and IL-12. 15 LYZ gene codes lysozyme, thus exerting antibacterial effect. TREM2 is a membrane protein that forms a receptor signalling complex with the TYRO protein.…”