Pathogen-Mediated Inhibition of Anorexia Promotes Host Survival and Transmission

Cell. 2017 Jan 26;168(3):503-516.e12. doi: 10.1016/j.cell.2017.01.006.


Sickness-induced anorexia is a conserved behavior induced during infections. Here, we report that an intestinal pathogen, Salmonella Typhimurium, inhibits anorexia by manipulating the gut-brain axis. Inhibition of inflammasome activation by the S. Typhimurium effector, SlrP, prevented anorexia caused by IL-1β-mediated signaling to the hypothalamus via the vagus nerve. Rather than compromising host defenses, pathogen-mediated inhibition of anorexia increased host survival. SlrP-mediated inhibition of anorexia prevented invasion and systemic infection by wild-type S. Typhimurium, reducing virulence while increasing transmission to new hosts, suggesting that there are trade-offs between transmission and virulence. These results clarify the complex and contextual role of anorexia in host-pathogen interactions and suggest that microbes have evolved mechanisms to modulate sickness-induced behaviors to promote health of their host and their transmission at the expense of virulence.

Keywords: IL-1β; Salmonella; Vagus nerve; inflammasome; pathogen transmission; sickness-induced anorexia; virulence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anorexia / microbiology*
  • Bacterial Proteins / metabolism
  • Host-Pathogen Interactions
  • Humans
  • Inflammasomes / immunology
  • Interleukin-1beta / immunology
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways
  • Salmonella Infections / immunology
  • Salmonella Infections / microbiology*
  • Salmonella Infections / transmission*
  • Salmonella typhimurium / pathogenicity*
  • Salmonella typhimurium / physiology
  • Specific Pathogen-Free Organisms
  • Virulence


  • Bacterial Proteins
  • Inflammasomes
  • Interleukin-1beta
  • SlrP protein, Salmonella typhimurium