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.
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.