The AP-1/JNK pathway is regulated by CD73 and gets dysregulated in aged hosts leading to defect in anti-pneumococcal function of neutrophils

We used high through put RNA-sequencing to identify changes in the PMN transcriptome induced by S. pneumoniae infection in order to gain further insight into the signaling pathways that are required for host response and are dysregulated in older individuals. PMNs were isolated from bone marrow of young WT, old WT and CD73KO mice and challenged with S.pneumonia TIGR4 strain in-vitro. Analysis of differentially expressed genes revealed that genes in AP-1/JNK pathway were upregulated in PMNs from CD73KO and old mice but not in PMNs from young mice. Inhibition of AP-1 and JNK using inhibitors boosted the anti-microbial actiivity of neutrophils from old and CD73KO mice. Overall design: Examination of age-related transcriptome changes in neutrophils isolated from young and old mice and challenged with S. pneumoniae