Our results indicate that (i) hemorrhage increases PN-induced morbidity and mortality, (ii) hemorrhage induces pDCs phenotypic alterations, as well as important defects in cDCs-induced T-cell proliferation (iii) CpG-ODN (TLR9 agonists) and MPLA (TLR-4 agonists) prevent hemorrhage-induced PN mortality, and restore the transcriptional activity of DCs. Here, TLR4 is linked to hemorrhage.