Persistently Active Microbial Molecules Prolong Innate Immune Tolerance In Vivo

PLoS Pathogens

Alan W. Varley¹  Robert S. Munford²  Mingfang Lu² 

[1] Infectious Diseases Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America;Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America

关键词: Macrophages;    Flow cytometry;    Peritoneum;    Gram negative bacteria;    Ascites;    Cytokines;    Cell staining;    Inflammation;   

DOI  :  10.1371/journal.ppat.1003339

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Measures that bolster the resolution phase of infectious diseases may offer new opportunities for improving outcome. Here we show that inactivation of microbial lipopolysaccharides (LPS) can be required for animals to recover from the innate immune tolerance that follows exposure to Gram-negative bacteria. When wildtype mice are exposed to small parenteral doses of LPS or Gram-negative bacteria, their macrophages become reprogrammed (tolerant) for a few days before they resume normal function. Mice that are unable to inactivate LPS, in contrast, remain tolerant for several months; during this time they respond sluggishly to Gram-negative bacterial challenge, with high mortality. We show here that prolonged macrophage reprogramming is maintained in vivo by the persistence of stimulatory LPS molecules within the cells' in vivo environment, where naïve cells can acquire LPS via cell-cell contact or from the extracellular fluid. The findings provide strong evidence that inactivation of a stimulatory microbial molecule can be required for animals to regain immune homeostasis following parenteral exposure to bacteria. Measures that disable microbial molecules might enhance resolution of tissue inflammation and help restore innate defenses in individuals recovering from many different infectious diseases.

【 授权许可】

CC BY