Type I and II interferons induce granulopoiesis and correlate with organ damage during infection-induced shock

Abstract The mechanisms that drive pathology in infection-induced shock are not well understood. tick-borne pathogen Ixodes ovatuserhlichia (IOE) induces severe inflammation, vascular damage, liver injury, and death. Mice lack the receptor for type I IFN, or receptors both II IFNs, improves survival by 50–70 90%, respectively. IOE infection induced a significant increase circulating granulocytes depended on IFNs. We also observed an IFN-dependent eosinophils basophils bone marrow IOE-infected C57BL/6TA (WT). Although IL-5 GM-CSF levels independent of IFN signaling, concentrations IL-3 IL-13, known to promote eosinophil differentiation survival, increased IFNAR-dependent manner. Furthermore, we demonstrate infection- CCL3 CCL5, two chemokines activation migration. While blood were increased, specific depletion WT at day 7 post-IOE infection, correlating with cell death pathology. In contrast, basophil frequencies mice. Additionally, Ifnar-deficient Ifnar-Ifngr-deficient mice exhibited normal reduced similar uninfected Together, our data reveal IFN-driven cytokine chemokine response correlates rampant granulopoiesis mortality provide evidence IFN-induced may contribute leak damage shock. Supported grants from NIH R35GM131842