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- W4313383604 abstract "Abstract Streptococcus pneumoniae is the most common cause of pneumonia, resulting in high morbidity and mortality worldwide despite advanced antimicrobial therapies and vaccines. Human individuals with constitutively active STING mutations have recurrent pneumococcal infections. Moreover, we found that mice lacking STING expression are more resistant to pulmonary S. pneumoniae infection compared to their wild-type controls. Here we investigated the role STING in the pathogenesis of pulmonary pneumococcal infection. We discovered two waves of IFNg production in the lung and IFNg at 48hrs, but not at 24hrs post-intra-nasal S. pneumoniae infection (hpi) is STING dependent. Using STING conditional knockouts, CCR2−/− and GREAT (interferon-Gamma Reporter with Endogenous polyA Transcript) mice, we found Ly6Chi monocytes to be the major contributors of lung IFNg production at 48hpi. Further, IFNg production requires cGAS-STING signaling pathway in Ly6Chi monocytes. IFNg stimulates inflammatory M1 macrophage polarization. We found STING−/− lung macrophages exhibit anti-inflammatory M2 like phenotype. We propose that cGAS-STING induces late stage IFNg in Ly6Chi monocytes to promote M1-like macrophage differentiation and exacerbate the pulmonary pneumococcal infection. Our novel findings a) Two distinct waves of IFNg production, b) cGAS-STING pathway in Ly6Chimonocytes but not macrophages induce lung IFNg production at 48hpi. How cGAS-STING signaling pathway induces IFNg production in monocytes will be discussed. The findings of this project will add substantial information to the role of IFNg in the host defense mechanism against S. pneumoniae and help design more effective treatment options." @default.
- W4313383604 created "2023-01-06" @default.
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- W4313383604 date "2018-05-01" @default.
- W4313383604 modified "2023-09-27" @default.
- W4313383604 title "cGAS-STING activation in Ly6Chi monocytes induces IFNg during pulmonary pneumococcal infection" @default.
- W4313383604 doi "https://doi.org/10.4049/jimmunol.200.supp.50.5" @default.
- W4313383604 hasPublicationYear "2018" @default.
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