Pathogen-Mediated Inhibition of Anorexia Promotes Host Survival and Transmission

被引：121

作者：

Rao, Sheila ^{[1
]}

Schieber, Alexandria M. Palaferri ^{[1
]}

O'Connor, Carolyn P. ^{[2
]}

Leblanc, Mathias ^{[3
]}

Michel, Daniela ^{[1
]}

Ayres, Janelle S. ^{[1
]}

机构：

[1] Salk Inst Biol Studies, Nomis Ctr Immunobiol & Microbial Pathogenesis, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA

[2] Salk Inst Biol Studies, Flow Cytometry Core Facil, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA

[3] Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA

来源：

CELL | 2017年 / 168卷 / 03期

关键词：

VAGUS NERVE; CALORIE RESTRICTION; DIETARY RESTRICTION; DISEASE TOLERANCE; DEFENSE STRATEGY; IMMUNE-RESPONSE; MANDUCA-SEXTA; C57BL/6; MICE; INFECTION; VIRULENCE;

D O I：

10.1016/j.cell.2017.01.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-1b-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.

引用

页码：503 / +

页数：26

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