The clinical and immunological performance of 28 days survival model of cecal ligation and puncture in humanized mice.

Abstract

Sepsis triggers a coordinated and thorough immune system response with long-term unfavorable sequelae after the initial insult. Long-term recovery from sepsis has garnered increasing attention recently, but a lack of suitable animal models impairs progress in this area. Our study, therefore, aimed to address the performance of the immune system in a survivable model of sepsis (cecal ligation and sepsis; CLP) for up to 28 d after the initial injury in humanized mice. Our model mimics human sepsis with weight loss and post-sepsis hypothermia. Within the first 7 d of sepsis, the M1 inflammatory cell subtype predominated, as evidenced by increased CD16 expression, but at 28 d, a mixed population of M1 and M2 inflammatory cells emerged, as evidenced by increased secretion of transforming growth factor TGFβ and CD206 expression. This change was accompanied by normalized production of interleukin (IL)-6, tumor necrosis factor TNFα and IL-10 at 28 d. Furthermore, the ability of MO to become regulatory DC or the frequency of endogenous DC were severely affected at 28 days. Thus, sepsis results in profound and persistent changes in the function of myeloid cells up to 28 days after CLP demonstrating the persistence of the new acquired immunological features long after resolution of the sepsis.