Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity

Denise Morais Da Fonseca, Timothy W. Hand, Seong Ji Han, Michael Y. Gerner, Arielle Glatman Zaretsky, Allyson L. Byrd, Oliver J. Harrison, Alexandra M. Ortiz, Mariam Quinones, Giorgio Trinchieri, Jason M. Brenchley, Igor E. Brodsky, Ronald N. Germain, Gwendalyn J. Randolph, Yasmine Belkaid

Research output: Contribution to journalArticlepeer-review

174 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)354-366
Number of pages13
JournalCell
Volume163
Issue number2
DOIs
StatePublished - Oct 8 2015

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