Effect And Mechanism Of Streptococcus Pneumonia On Susceptibility To Asthma In Mice Of Different Ages

Background:Asthma is the most common chronic airway inflammatory disease among children in the world,and the majority of adult asthma originates in childhood,indicating that early-life events have important role in asthma pathogenesis.Streptococcus pneumoniae is the most common bacterial pathogen of community-acquired pneumonia in young children.Growing evidence links Streptococcus pneumoniae(S.pneumoniae)infection with the development and exacerbation of asthma in children.While,researches demonstrated that S.pneumoniae infection in adulthood BALB/c mice suppressed allergic asthma hallmarks.Objective:To investigate the effects and mechanisms of S.pneumoniae infection at different ages on asthma in later life.Methods:Neonatal,infantile,and adult BALB/c mice were infected with S.pneumoniae,sensitized and challenged with ovalbumin 3 weeks after infection.The airway hyperresponsiveness(AHR),severity of inflammation in lung tissue,number of total cells,differential cell counts and expression of cytokines in bronchoalveolar lavage fluid(BALF),percentages of CD4~+T cells and CD103~+DCs,and IDO expression in lung tissue were assayed within 24 hours after the final challenge,compared with uninfected allergic and nonallergic controls.Results:Neonatal S.pneumoniae infection enhanced the development of hallmark features of asthma in ovalbumin-induced allergic airways disease.Notably,neonatal S.pneumoniae infection promoted airway hyperresponsiveness,the inflammation of lung tissues,leukocytes(especially neutrophils)influx and the Th17 cells response,inhibited development of Foxp3~+Treg,the expression of IDO in lungs and CD11c~+CD103~+DCs.However,infantile S.pneumoniae infection had no effects on the expression of IDO and susceptibility of asthma.By contrast,adult S.pneumoniae infection attenuated the features of allergic inflammation with reduced airway hyperresponsiveness,leukocytes and Th2cells response,increased Foxp3~+Treg cells response and IDO in lungs and CD11c~+CD103~+DCs.Conclusion:Neonatal S.pneumoniae infection promoted asthma development by inhibiting IDO expression,while adult S.pneumoniae infection protected from asthma development by inducing IDO production.