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

Pathogen-Mediated Inhibition of Anorexia Promotes Host Survival and Transmission.

Author information

1
Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
2
Flow Cytometry Core Facility, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
3
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
4
Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: jayres@salk.edu.

Abstract

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

PMID:
28129542
PMCID:
PMC5324724
DOI:
10.1016/j.cell.2017.01.006
[Indexed for MEDLINE]
Free PMC Article

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