期刊
JOURNAL OF IMMUNOLOGY
卷 209, 期 3, 页码 548-558出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2200110
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This study focused on Pseudomonas aeruginosa infections of the cornea and found that IL-1 alpha plays a significant role in impairing bacterial clearance.
Pseudomonas aeruginosa is an important cause of dermal, pulmonary, and ocular disease. Our studies have focused on P. aeruginosa infections of the cornea (keratitis) as a major cause of blinding microbial infections. The infection leads to an influx of innate immune cells, with neutrophils making up to 90% of recruited cells during early stages. We previously reported that the proinflammatory cytokines IL-1 alpha and IL-1 beta were elevated during infection. Compared with wild-type (WT), infected Il1b(-/-) mice developed more severe corneal disease that is associated with impaired bacterial killing as a result of defective neutrophil recruitment. We also reported that neutrophils are an important source of IL-1 alpha and IL-1 beta, which peaked at 24 h postinfection. To examine the role of IL-1 alpha compared with IL-1 beta in P. aeruginosa keratitis, we inoculated corneas of C57BL/6 (WT), Il1a(-/-),( )Il1b(-/-) and Il1a(-/-)( )Il1b(-/-)(double-knockout) mice with 5 x 10(4) ExoS-expressing P. aeruginosa. Il1b(-/- )and double-knockout mice have significantly higher bacterial burden that was consistent with delayed neutrophil and monocyte recruitment to the corneas. Surprisingly, Il1a(-/- )mice had the opposite phenotype with enhanced bacteria clearance compared with WT mice. Although there were no significant differences in neutrophil recruitment, Il1a(-/- )neutrophils displayed a more proinflammatory transcriptomic profile compared to WT with elevations in C1q expression that likely caused the phenotypic differences observed. To our knowledge, our findings identify a novel, non-redundant role for IL-1 alpha in impairing bacterial clearance.
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