TY - JOUR
T1 - Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity
AU - Fonseca, Denise Morais Da
AU - Hand, Timothy W.
AU - Han, Seong Ji
AU - Gerner, Michael Y.
AU - Zaretsky, Arielle Glatman
AU - Byrd, Allyson L.
AU - Harrison, Oliver J.
AU - Ortiz, Alexandra M.
AU - Quinones, Mariam
AU - Trinchieri, Giorgio
AU - Brenchley, Jason M.
AU - Brodsky, Igor E.
AU - Germain, Ronald N.
AU - Randolph, Gwendalyn J.
AU - Belkaid, Yasmine
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/10/8
Y1 - 2015/10/8
N2 - Infections have been proposed as initiating factors for inflammatory disorders; however, identifying associations between defined infectious agents and the initiation of chronic disease has remained elusive. Here, we report that a single acute infection can have dramatic and long-term consequences for tissue-specific immunity. Following clearance of Yersinia pseudotuberculosis, sustained inflammation and associated lymphatic leakage in the mesenteric adipose tissue deviates migratory dendritic cells to the adipose compartment, thereby preventing their accumulation in the mesenteric lymph node. As a consequence, canonical mucosal immune functions, including tolerance and protective immunity, are persistently compromised. Post-resolution of infection, signals derived from the microbiota maintain inflammatory mesentery remodeling and consequently, transient ablation of the microbiota restores mucosal immunity. Our results indicate that persistent disruption of communication between tissues and the immune system following clearance of an acute infection represents an inflection point beyond which tissue homeostasis and immunity is compromised for the long-term.
AB - Infections have been proposed as initiating factors for inflammatory disorders; however, identifying associations between defined infectious agents and the initiation of chronic disease has remained elusive. Here, we report that a single acute infection can have dramatic and long-term consequences for tissue-specific immunity. Following clearance of Yersinia pseudotuberculosis, sustained inflammation and associated lymphatic leakage in the mesenteric adipose tissue deviates migratory dendritic cells to the adipose compartment, thereby preventing their accumulation in the mesenteric lymph node. As a consequence, canonical mucosal immune functions, including tolerance and protective immunity, are persistently compromised. Post-resolution of infection, signals derived from the microbiota maintain inflammatory mesentery remodeling and consequently, transient ablation of the microbiota restores mucosal immunity. Our results indicate that persistent disruption of communication between tissues and the immune system following clearance of an acute infection represents an inflection point beyond which tissue homeostasis and immunity is compromised for the long-term.
UR - http://www.scopus.com/inward/record.url?scp=84943653785&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2015.08.030
DO - 10.1016/j.cell.2015.08.030
M3 - Article
C2 - 26451485
AN - SCOPUS:84943653785
SN - 0092-8674
VL - 163
SP - 354
EP - 366
JO - Cell
JF - Cell
IS - 2
ER -