title: Pathogen-Mediated Inhibition of Anorexia Promotes Host Survival and Transmission.
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.
authors.affiliation: Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Rao
authors.affiliation: Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Alexandria M Palaferri
authors.initials: AMP
authors.lastname: Schieber
authors.affiliation: Flow Cytometry Core Facility, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Carolyn P
authors.initials: CP
authors.lastname: O'Connor
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Mathias
authors.initials: M
authors.lastname: Leblanc
authors.affiliation: Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Michel
authors.affiliation: Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: jayres@salk.edu.
authors.forename: Janelle S
authors.initials: JS
authors.lastname: Ayres
mesh_terms: D000818:Animals; D000855:Anorexia / Q000382:microbiology*; D001426:Bacterial Proteins / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D058847:Inflammasomes / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways; D012480:Salmonella Infections / Q000276:immunology / Q000382:microbiology* / Q000635:transmission*; D012486:Salmonella typhimurium / Q000472:pathogenicity* / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; C401846:SlrP protein, Salmonella typhimurium
keywords: IL-1β; Salmonella; Vagus nerve; inflammasome; pathogen transmission; sickness-induced anorexia; virulence