Severe traumatic hemorrhagic shock induces compromised immune barrier function of the mesenteric lymph node leading to an increase in intestinal bacterial translocation.

Critically ill patients have increased susceptibility to translocation of gut bacteria. However, the mechanisms are complicated and remain unclear, and the aim of this study was to explore these mechanisms. Rats exposed to different levels of shock were orally administrated with bioluminescent Citrobacter. We found that severe shock caused an increase in bacterial translocation to the visceral organs, such as liver, spleen and blood, compared with mild shock. Surprisingly, bacterial translocation to mesenteric lymph node (MLN) was unchanged between the two shock groups. Various methods, including flow cytometry, a co-culture model and western blots, were used to evaluate MLN-associated immune function. Specifically, we focused on mesenteric lymph node dendritic cells (MLN-DCs), the critical antigen presenting cells involved in the construction of the immune barrier in MLN. We also found that severe shock impaired the phenotypic maturation of MLN-DCs and induced a tolerogenic phenotype. Furthermore, co-culture assays of DCs with naive CD4(+) T cells showed that DCs subject to severe shock were more inclined to polarize native CD4(+) T cells into Th2 and Treg cells. This study successfully reproduced the clinical phenomenon of severe shock resulting in increased bacterial translocation to extraintestinal tissues, and this may be related to the compromised immune barrier function of MLN, as maturation and function of MLN-DC's were badly impaired.