The cytokine MIF controls daily rhythms of symbiont nutrition in an animal-bacterial association

Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27578-27586. doi: 10.1073/pnas.2016864117. Epub 2020 Oct 16.


The recent recognition that many symbioses exhibit daily rhythms has encouraged research into the partner dialogue that drives these biological oscillations. Here we characterized the pivotal role of the versatile cytokine macrophage migration inhibitory factor (MIF) in regulating a metabolic rhythm in the model light-organ symbiosis between Euprymna scolopes and Vibrio fischeri As the juvenile host matures, it develops complex daily rhythms characterized by profound changes in the association, from gene expression to behavior. One such rhythm is a diurnal shift in symbiont metabolism triggered by the periodic provision of a specific nutrient by the mature host: each night the symbionts catabolize chitin released from hemocytes (phagocytic immune cells) that traffic into the light-organ crypts, where the population of V. fischeri cells resides. Nocturnal migration of these macrophage-like cells, together with identification of an E. scolopes MIF (EsMIF) in the light-organ transcriptome, led us to ask whether EsMIF might be the gatekeeper controlling the periodic movement of the hemocytes. Western blots, ELISAs, and confocal immunocytochemistry showed EsMIF was at highest abundance in the light organ. Its concentration there was lowest at night, when hemocytes entered the crypts. EsMIF inhibited migration of isolated hemocytes, whereas exported bacterial products, including peptidoglycan derivatives and secreted chitin catabolites, induced migration. These results provide evidence that the nocturnal decrease in EsMIF concentration permits the hemocytes to be drawn into the crypts, delivering chitin. This nutritional function for a cytokine offers the basis for the diurnal rhythms underlying a dynamic symbiotic conversation.

Keywords: Euprymna scolopes; Vibrio fischeri; daily cycling; symbiont metabolism; symbiosis.

Publication types

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

MeSH terms

  • Aliivibrio fischeri / metabolism*
  • Animals
  • Cell Movement
  • Chitin / metabolism
  • Circadian Rhythm / physiology*
  • Decapodiformes / microbiology
  • Decapodiformes / physiology*
  • Female
  • Hemocytes / metabolism
  • Host Microbial Interactions / physiology*
  • Macrophage Migration-Inhibitory Factors / metabolism*
  • Nutrients / metabolism
  • Peptidoglycan / metabolism
  • Symbiosis / physiology


  • Macrophage Migration-Inhibitory Factors
  • Peptidoglycan
  • Chitin