IL-17A在高耐药且高毒力金黄色葡萄球菌急性吸入性肺炎中的作用OA

Objective To investigate the role of interleukin(IL)-17A in acute inhalational pneumonia induced by the highly drug-resistant and hypervirulent Staphylococcus aureus strain USA300-R in mice.Methods An acute in-halational pneumonia model was established in mice using an aerosolized pulmonary delivery technique.RNA se-quencing(RNA-seq)and enzyme-linked immunosorbent assay(ELISA)were employed to examine the expression dynamics of Il17a mRNA and IL-17A protein,respectively,in the lungs of infected mice.Il17a knockout(Il17a-/-)mice were generated using CRISPR/Cas9 gene editing technology.The survival rate,body weight,bacte-rial load in lung tissue,and histopathological changes were compared between Il17a-/-and wild-type(WT)mice following inhalational infection with USA300-R.Results 12 hours after USA300-R infection,compared to pre-infection,the expression level of Il17a mRNA in lung tissue and the level of IL-17A protein in bronchoalveolar la-vage fluid(BALF)increased by approximately 50-fold(P<0.01)and 6-fold(P<0.001),respectively.Compared to WT mice,Il17a-/-mice exhibited approximately 10-fold higher bacterial loads in lung tissue at both 12 and 24 hours post-infection(P<0.001,P<0.05).However,they showed significantly attenuated lung histopathological injury,reduced alveolar wall thickening,markedly decreased neutrophil infiltration,and an approximately 50%improvement in survival rate(P<0.05).Conclusion In acute Staphylococcus aureus USA300-R inhalational pneumonia,IL-17A contributes to bacterial clearance by recruiting neutrophils;however,excessive neutrophil in-filtration exacerbates pulmonary inflammation and injury,reduces survival rates,and represents a potential thera-peutic target.