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- W4313404814 abstract "Abstract Severe infection dramatically alters blood production, but the mechanisms impacting hematopoietic stem and progenitor cell (HSC/HSPC) recovery have not been carefully investigated. Using Ixodes ovatus Ehrlichia (IOE), a pathogen that causes severe shock-like illness and bone marrow (BM) aplasia, we explored the kinetics and mechanisms of hematopoietic recovery. Doxycycline treatment is necessary to prevent IOE-induced death and control bacterial burden in mice, but is not sufficient to prevent HSC/HSPC loss. During recovery from acute infection (12dpi) we saw increased cellularity of LT-HSCs and MPPs, accompanied by diminished function measured by decreased colony forming units (CFUs) in methocult assays. Reduced CFUs indicate a deficiency in BM myelopoietic function during recovery phase post- IOE. We previously showed that IL-18R-deficient mice exhibited improved CFUs at 12dpi, suggesting IL-18R signaling is detrimental to recovery from shock-like IOE. Utilizing a mixed BM chimeric mouse model (50:50 WT:IL-18R−/−), we observed that during recovery at 15dpi, IL-18R−/− cellularity predominates the LT-HSC and MPP2 populations, demonstrating an intrinsic role for IL-18R in limiting recovery of these populations. Additionally, BM chimeras at 15dpi showed increased levels of cell death (Annexin V+ and 7AAD+) in WT HSCs compared with IL-18R−/− HSCs. Transplantation of whole BM from mixed BM chimeric mice revealed a pronounced bias for IL-18R−/− cells, indicating that IL-18R−/− cells had a competitive advantage and improved function after IOE infection. Together, these data support the conclusion that IL-18R signaling impairs HSC function during recovery from severe, shock-like infection via decreased HSC viability. This work was supported by National Institutes of Health funding from NIGMS (R35GM131842) to KCM." @default.
- W4313404814 created "2023-01-06" @default.
- W4313404814 creator A5010378962 @default.
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- W4313404814 date "2022-05-01" @default.
- W4313404814 modified "2023-09-27" @default.
- W4313404814 title "IL-18R signaling impairs hematopoietic recovery after severe, shock-like infection" @default.
- W4313404814 doi "https://doi.org/10.4049/jimmunol.208.supp.47.03" @default.
- W4313404814 hasPublicationYear "2022" @default.
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