The gut flora is required for the control of intestinal infection by poly(I:C) administration in neonates.

We found that immunostimulation of the intestinal immune system of neonatal mice by poly(I:C) injection decreased intestinal infection by the parasite Cryptosporidium parvum. We showed that the presence of dendritic cells and the cooperation of mutually dependent cytokines, such as IL-12p40, and type I and type II IFNs, were involved in the mechanism of protection induced by poly(I:C). This protection is dependent not only on TLR3-TRIF signaling, but also on the activation of the TLR5-MyD88 pathway by gut microbiota. These results raise the possibility that flagellated intestinal commensal bacteria may, in the presence of natural or synthetic agonists of TLR3, provide synergy between the TRIF and MyD88 signaling pathways, thereby favoring the development of mucosal defenses. In this addendum, we summarize these recent findings and discuss their implications for neonatal infections and immunomodulatory strategies.