Long Term Impact of Acute Infection on Lymphatic Function

Abstract

Abstract The lymphatic system facilitates critical processes for immunity, including immune cell trafficking, lipid transport, and the maintenance of tissue homeostasis. In the mesentery, these lymphatic vessels (LVs) allow drainage and cell trafficking from the gastrointestinal (GI) tract through the mesenteric adipose tissue (mAT) to the mesenteric lymph nodes (mLNs). During GI infection, this vasculature is altered by inflammation, which can induce lymphatic leakage. Repair of LVs after infection is resolved is necessary to restore lymphatic function. Although preliminary studies have found acute lymphatic leakage is conserved between GI pathogens, in an acute Yersinia pseudotuberculosis infection, mice control bacterial growth, but develop a chronic mesenteric lymphadenopathy and the increased permeability of LVs does not resolve after the infection is cleared. Consequently, the migratory CD103+CD11b+dendritic cells (DP DCs) cannot reach the mLN and instead pass through the dysregulated LVs into the mAT. The absence of DP DCs in the mLN is associated with impaired development of Th17 adaptive immunity to oral vaccination. Little is known about the mechanisms that regulate lymphatic integrity, however these studies reveal a remodeling of the adipose tissue after infection, and are ongoing to understand the long-term increased permeability of LVs and the potential to restore function. Our results support the idea that acute GI infections are associated with permanent changes in DC traffic, which interfere with the activation of immune responses and can have severe implications for GI tract integrity and predisposition to inflammatory diseases and suggest that dysregulation of the mAT may contribute to the prolonged disruption.