Using the colon ascendens stent peritonitis (CASP) model, we demonstrate that IFNβ<sup>-/-</sup> and type I IFN receptor (IFNAR1)<sup>-/-</sup> mice were less susceptible to sepsis after pre-stimulation with the viral mimetic poly(I:C).
Then, Caco-2 monolayers were utilized to further investigate the protective effect of the EcN supernatant (EcN<sup>sup</sup>) on the barrier dysfunction induced by TNF-<i>α</i> and IFN-<i>γ</i> in vitro; the plasma level of both the cytokines increased significantly during sepsis.
In this preliminary study, we identified a cluster of cytokines involved in innate inflammatory response associated with septic myocardial dysfunction and organ failures, whereas the IL-17/IFN pathway was associated with a faster sepsis resolution and a better survival.
Here, we demonstrate that sunitinib/erlotinib combination achieves sustained suppression of systemic infection at approved dose in DENV-infected IFN-α/β and IFN-γ receptor-deficient mice.
Interestingly, in a model of lipopolysaccharide-induced septic shock, selective <i>Irf3</i> deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4-IRF3 type I IFN axis in this model of sepsis.
We conclude that a well-regulated IFN response, with the ability to overcome early viral immune inhibition, without hyperinflammation, contributes to the ability of ducks to survive H5N1 influenza replication in their airways, and yet clear systemic infection and limit disease.