The evolutionary ecology of circadian rhythms in infection

Abstract

Biological rhythms coordinate organisms’ activities with daily rhythms in the environment. For parasites, this includes rhythms in both the external abiotic environment and the within-host biotic environment. Hosts exhibit rhythms in behaviours and physiologies, including immune responses, and parasites exhibit rhythms in traits underpinning virulence and transmission. Yet, the evolutionary and ecological drivers of rhythms in traits underpinning host defence and parasite offence are largely unknown. Here, we explore how hosts use rhythms to defend against infection, why parasites have rhythms and whether parasites can manipulate host clocks to their own ends. Harnessing host rhythms or disrupting parasite rhythms could be exploited for clinical benefit; we propose an interdisciplinary effort to drive this emerging field forward.

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References

  1. 1.

    de Mairan, J. Observation botanique. Hist. l’Academie R. des Sci. Paris (1729).

  2. 2.

    Sharma, V. K. Adaptive significance of circadian clocks. Chronobiol. Int. 20, 901–919 (2003).

  3. 3.

    Green, R. M., Tingay, S., Wang, Z.-Y. & Tobin, E. M. Circadian rhythms confer a higher level of fitness to Arabidopsis plants. Plant Physiol. 129, 576–584 (2002).

  4. 4.

    Helm, B. et al. Two sides of a coin: ecological and chronobiological perspectives of timing in the wild. Philos. Trans. R. Soc. B Biol. Sci. 372, 20160246 (2017).

  5. 5.

    Scheiermann, C., Gibbs, J., Ince, L. & Loudon, A. Clocking in to immunity. Nat. Rev. Immunol. 18, 423–437 (2018).

  6. 6.

    Martinez-Bakker, M. & Helm, B. The influence of biological rhythms on host–parasite interactions. Trends Ecol. Evol. 30, 314–326 (2015).

  7. 7.

    Reece, S. E., Prior, K. F. & Mideo, N. The life and times of parasites: rhythms in strategies for within-host survival and between-host transmission. J. Biol. Rhythms 32, 516–533 (2017).

  8. 8.

    Rijo-Ferreira, F., Pinto-Neves, D., Barbosa-Morais, N. L., Takahashi, J. S. & Figueiredo, L. M. Trypanosoma brucei metabolism is under circadian control. Nat. Microbiol. 2, 17032 (2017).

  9. 9.

    Scheiermann, C., Kunisaki, Y. & Frenette, P. S. Circadian control of the immune system. Nat. Rev. Immunol. 13, 190–198 (2013).

  10. 10.

    Curtis, A. M., Bellet, M. M., Sassone-Corsi, P. & O’Neill, L. A. J. Circadian clock proteins and immunity. Immunity 40, 178–186 (2014).

  11. 11.

    Zasłona, Z. et al. The circadian protein BMAL1 in myeloid cells is a negative regulator of allergic asthma. Am. J. Physiol. Lung Cell Mol. Physiol. 312, L855–L860 (2017).

  12. 12.

    Keller, M. et al. A circadian clock in macrophages controls inflammatory immune responses. Proc. Natl Acad. Sci. 106, 21407–21412 (2009).

  13. 13.

    Nguyen, K. D. et al. Circadian gene Bmal1 regulates diurnal oscillations of Ly6Chi inflammatory monocytes. Science 341, 1483–1488 (2013).

  14. 14.

    Haus, E. & Smolensky, M. H. Biologic rhythms in the immune system. Chronobiol. Int. 16, 581–622 (1999).

  15. 15.

    Haus, E., Lakatua, D. J., Swoyer, J. & Sackett-Lundeen, L. Chronobiology in hematology and immunology. Am. J. Anat. 168, 467–517 (1983).

  16. 16.

    Labrecque, N. & Cermakian, N. Circadian clocks in the immune system. J. Biol. Rhythms 30, 277–290 (2015).

  17. 17.

    Graham, A. L., Allen, J. E. & Read, A. F. Evolutionary causes and consequences of immunopathology. Annu. Rev. Ecol. Evol. Syst. 36, 373–397 (2005).

  18. 18.

    Kerr, A. M., Gershman, S. N. & Sakaluk, S. K. Experimentally induced spermatophore production and immune responses reveal a trade-off in crickets. Behav. Ecol. 21, 647–654 (2010).

  19. 19.

    Roden, L. C. & Ingle, R. A. Lights, rhythms, infection: the role of light and the circadian clock in determining the outcome of plant–pathogen interactions. Plant Cell 21, 2546–2552 (2009).

  20. 20.

    Bhardwaj, V., Meier, S., Petersen, L. N., Ingle, R. A. & Roden, L. C. Defence responses of Arabidopsis thaliana to infection by Pseudomonas syringae are regulated by the circadian clock. PLoS One 6, e26968 (2011).

  21. 21.

    Ingle, R. A. et al. Jasmonate signalling drives time-of-day differences in susceptibility of Arabidopsis to the fungal pathogen Botrytis cinerea. Plant J. 84, 937–948 (2015).

  22. 22.

    Bellet, M. M. et al. Circadian clock regulates the host response to Salmonella. Proc. Natl Acad. Sci. 110, 9897–9902 (2013).

  23. 23.

    Kiessling, S. et al. The circadian clock in immune cells controls the magnitude of Leishmania parasite infection. Sci. Rep. 7, 10892 (2017).

  24. 24.

    Zuk, M., Rotenberry, J. T. & Tinghitella, R. M. Silent night: adaptive disappearance of a sexual signal in a parasitized population of field crickets. Biol. Lett. 2, 521–524 (2006).

  25. 25.

    Levri, E. P. & Lively, C. M. The effects of size, reproductive condition, and parasitism on foraging behaviour in a freshwater snail, Potamopyrgus antipodarum. Anim. Behav. 51, 891–901 (1996).

  26. 26.

    Ponton, F. et al. Water-seeking behavior in worm-infected crickets and reversibility of parasitic manipulation. Behav. Ecol. 22, 392–400 (2011).

  27. 27.

    Hopwood, T. W. et al. The circadian regulator BMAL1 programmes responses to parasitic worm infection via a dendritic cell clock. Sci. Rep. 8, 3782 (2018).

  28. 28.

    Johnson, C. H., Zhao, C., Xu, Y. & Mori, T. Timing the day: what makes bacterial clocks tick? Nat. Rev. Microbiol. 15, 232–242 (2017).

  29. 29.

    Zuk, M., Simmons, L. & Cupp, L. Calling characteristics of parasitized and unparasitized populations of the field cricket Teleogryllus oceanicus. Behav. Ecol. Sociobiol. 33, 339–343 (1993).

  30. 30.

    Clark, I. A., Budd, A. C. & Alleva, L. M. Sickness behaviour pushed too far—the basis of the syndrome seen in severe protozoal, bacterial and viral diseases and post-trauma. Malar. J. 7, 208 (2008).

  31. 31.

    Dantzer, R., O’Connor, J. C., Freund, G. G., Johnson, R. W. & Kelley, K. W. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat. Rev. Neurosci. 9, 46–56 (2008).

  32. 32.

    Ghai, R. R., Fugère, V., Chapman, C. A., Goldberg, T. L. & Davies, T. J. Sickness behaviour associated with non-lethal infections in wild primates. Proc. Biol. Sci. 282, 20151436 (2015).

  33. 33.

    Kluger, M. J. Phylogeny of fever. Fed. Proc. 38, 30–34 (1979).

  34. 34.

    Evans, S. S., Repasky, E. A. & Fisher, D. T. Fever and the thermal regulation of immunity: the immune system feels the heat. Nat. Rev. Immunol. 15, 335–349 (2015).

  35. 35.

    Kluger, M. J., Ringler, D. H. & Anver, M. R. Fever and survival. Science 188, 166–168 (1975).

  36. 36.

    Schulman, C. I. et al. The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study. Surg. Infect. (Larchmt.) 6, 369–375 (2005).

  37. 37.

    Earn, D. J. D., Andrews, P. W. & Bolker, B. M. Population-level effects of suppressing fever. Proc. Biol. Sci. 281, 20132570 (2014).

  38. 38.

    Levi, F. & Schibler, U. Circadian rhythms: mechanisms and therapeutic implications. Annu. Rev. Pharmacol. Toxicol. 47, 593–628 (2007).

  39. 39.

    Matthews, J. H., Marte, E. & Halberg, F. A circadian susceptibility–resistance cycle to fluothane in male B 1 mice. Can. Anaesth. Soc. J. 11, 280–290 (1964).

  40. 40.

    Zhang, R., Lahens, N. F., Ballance, H. I., Hughes, M. E. & Hogenesch, J. B. A circadian gene expression atlas in mammals: implications for biology and medicine. Proc. Natl Acad. Sci. USA 111, 16219–16224 (2014).

  41. 41.

    Hawking, F. The 24-hour periodicity of microfilariae: biological mechanisms responsible for its production and control. Proc. R. Soc. Lond. B Biol. Sci. 169, 59–76 (1967).

  42. 42.

    Mouahid, G. et al. A new chronotype of Schistosoma mansoni: adaptive significance. Trop. Med. Int. Health 17, 727–732 (2012).

  43. 43.

    Martinaud, G., Billaudelle, M. & Moreau, J. Circadian variation in shedding of the oocysts of Isospora turdi (Apicomplexa) in blackbirds (Turdusmerula): an adaptative trait against desiccation and ultraviolet radiation. Int. J. Parasitol. 39, 735–739 (2009).

  44. 44.

    Prior, K. F. et al. Timing of host feeding drives rhythms in parasite replication. PLoS Pathog. 14, e1006900 (2018).

  45. 45.

    Hirako, I. C. et al. Daily rhythms of TNFα expression and food intake regulate synchrony of Plasmodium stages with the host circadian cycle. Cell Host Microbe 23, 796–808.e6 (2018).

  46. 46.

    Reece, S. E. & Prior, K. F. Malaria makes the most of mealtimes. Cell Host Microbe 23, 695–697 (2018).

  47. 47.

    Fenske, M. P., Nguyen, L. P., Horn, E. K., Riffell, J. A. & Imaizumi, T. Circadian clocks of both plants and pollinators influence flower seeking behavior of the pollinator hawkmoth Manduca sexta. Sci. Rep. 8, 2842 (2018).

  48. 48.

    Kharouba, H. M. et al. Global shifts in the phenological synchrony of species interactions over recent decades. Proc. Natl Acad. Sci. USA 115, 5211–5216 (2018).

  49. 49.

    Hevia, M. A., Canessa, P., Müller-Esparza, H. & Larrondo, L. F. A circadian oscillator in the fungus Botrytis cinerea regulates virulence when infecting Arabidopsis thaliana. Proc. Natl Acad. Sci. USA 112, 8744–8749 (2015).

  50. 50.

    Rensing, L., Meyer-Grahle, U. & Ruoff, P. Biological timing and the clock metaphor: oscillatory and hourglass mechanisms. Chronobiol. Int. 18, 329–369 (2001).

  51. 51.

    Mrosovsky, N. Masking: history, definitions, and measurement. Chronobiol. Int. 16, 415–429 (1999).

  52. 52.

    Sougoufara, S. et al. Biting by Anopheles funestus in broad daylight after use of long-lasting insecticidal nets: a new challenge to malaria elimination. Malar. J. 13, 125 (2014).

  53. 53.

    Rund, S. S. C., O’Donnell, A. J., Gentile, J. E. & Reece, S. E. Daily rhythms in mosquitoes and their consequences for malaria transmission. Insects 7, 14 (2016).

  54. 54.

    Schneider, P. et al. Adaptive periodicity in the infectivity of malaria gametocytes to mosquitoes. Proc. Biol. Sci. 285, 294942 (2018).

  55. 55.

    Pigeault, R., Caudron, Q., Nicot, A., Rivero, A. & Gandon, S. Timing malaria transmission with mosquito fluctuations. Evol. Lett. 2, 378–389 (2018).

  56. 56.

    Thomas, F., Rigaud, T. & Brodeur, J. in Encyclopedia of Animal Behavior (eds. Breed, M. & Moore, J.) 661–669 (Elsevier, 2010).

  57. 57.

    de Bekker, C., Merrow, M. & Hughes, D. P. From behavior to mechanisms: an integrative approach to the manipulation by a parasitic fungus (Ophiocordyceps unilateralis s.l.) of its host ants (Camponotus spp.). Integr. Comp. Biol. 54, 166–176 (2014).

  58. 58.

    Ko, C. H. & Takahashi, J. S. Molecular components of the mammalian circadian clock. Hum. Mol. Genet. 15, R271–R277 (2006).

  59. 59.

    Rijo-Ferreira, F. et al. Sleeping sickness is a circadian disorder. Nat. Commun. 9, 62 (2018).

  60. 60.

    Edgar, R. S. et al. Cell autonomous regulation of herpes and influenza virus infection by the circadian clock. Proc. Natl Acad. Sci. USA 113, 10085–10090 (2016).

  61. 61.

    Thomas, F. et al. Do hairworms (Nematomorpha) manipulate the water seeking behaviour of their terrestrial hosts? J. Evol. Biol. 15, 356–361 (2002).

  62. 62.

    Biron, D. G. et al. ‘Suicide’ of crickets harbouring hairworms: a proteomics investigation. Insect Mol. Biol. 15, 731–742 (2006).

  63. 63.

    Hughes, M. E. et al. Guidelines for genome-scale analysis of biological rhythms. J. Biol. Rhythms 32, 380–393 (2017).

  64. 64.

    Lively, C. M. Evidence from a New Zealand snail for the maintenance of sex by parasitism. Nature 328, 519 (1987).

  65. 65.

    Levri, E. P. Parasite-induced change in host behavior of a freshwater snail: parasitic manipulation or byproduct of infection? Behav. Ecol. 10, 234–241 (1999).

  66. 66.

    Hoover, K. et al. A gene for an extended phenotype. Science 333, 1401 (2011).

  67. 67.

    Goulson, D. Wipfelkrankheit: modification of host behaviour during baculoviral infection. Oecologia 109, 219–228 (1997).

  68. 68.

    de Bekker, C. et al. Gene expression during zombie ant biting behavior reflects the complexity underlying fungal parasitic behavioral manipulation. BMC Genomics 16, 620 (2015).

  69. 69.

    de Bekker, C., Will, I., Das, B. & Adams, R. M. M. The ants (Hymenoptera: Formicidae) and their parasites: effects of parasitic manipulations and host responses on ant behavioral ecology. Myrmecol. News 28, 1–24 (2018).

  70. 70.

    Herbison, R., Lagrue, C. & Poulin, R. The missing link in parasite manipulation of host behaviour. Parasit. Vectors 11, 222 (2018).

  71. 71.

    Spoelstra, K., Wikelski, M., Daan, S., Loudon, A. S. I. & Hau, M. Natural selection against a circadian clock gene mutation in mice. Proc. Natl Acad. Sci. USA 113, 686–691 (2016).

  72. 72.

    Stone, E. F. et al. The circadian clock protein timeless regulates phagocytosis of bacteria in Drosophila. PLoS Pathog. 8, e1002445 (2012).

  73. 73.

    Lee, J.-E. & Edery, I. Circadian regulation in the ability of Drosophila to combat pathogenic infections. Curr. Biol. 18, 195–199 (2008).

  74. 74.

    van der Vinne, V. et al. Cold and hunger induce diurnality in a nocturnal mammal. Proc. Natl Acad. Sci. USA 111, 15256–15260 (2014).

  75. 75.

    Bloch, G. & Robinson, G. E. Chronobiology. Reversal of honeybee behavioural rhythms. Nature 410, 1048 (2001).

  76. 76.

    Bulla, M. et al. Unexpected diversity in socially synchronized rhythms of shorebirds. Nature 540, 109–113 (2016).

  77. 77.

    Gibbs, J. E. et al. The nuclear receptor REV-ERBα mediates circadian regulation of innate immunity through selective regulation of inflammatory cytokines. Proc. Natl Acad. Sci. USA 109, 582–587 (2012).

  78. 78.

    Marpegan, L. et al. Diurnal variation in endotoxin-induced mortality in mice: correlation with proinflammatory factors. Chronobiol. Int. 26, 1430–1442 (2009).

  79. 79.

    Gibbs, J. et al. An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action. Nat. Med. 20, 919–926 (2014).

  80. 80.

    Druzd, D. et al. Lymphocyte circadian clocks control lymph node trafficking and adaptive immune responses. Immunity 46, 120–132 (2017).

  81. 81.

    Gagnidze, K. et al. Nuclear receptor REV-ERBα mediates circadian sensitivity to mortality in murine vesicular stomatitis virus-induced encephalitis. Proc. Natl Acad. Sci. USA 113, 5730–5735 (2016).

  82. 82.

    Kuo, T.-H., Pike, D. H., Beizaeipour, Z. & Williams, J. A. Sleep triggered by an immune response in Drosophila is regulated by the circadian clock and requires the NFκβ relish. BMC Neurosci. 11, 17 (2010).

  83. 83.

    Murdock, C. C., Moller-Jacobs, L. L. & Thomas, M. B. Complex environmental drivers of immunity and resistance in malaria mosquitoes. Proc. Biol. Sci. 280, 20132030 (2013).

  84. 84.

    Griebel, T. & Zeier, J. Light regulation and daytime dependency of inducible plant defenses in Arabidopsis: phytochrome signaling controls systemic acquired resistance rather than local defense. Plant Physiol. 147, 790–801 (2008).

  85. 85.

    Korneli, C., Danisman, S. & Staiger, D. Differential control of pre-invasive and post-invasive antibacterial defense by the Arabidopsis circadian clock. Plant Cell Physiol. 55, 1613–1622 (2014).

  86. 86.

    Wang, W. et al. Timing of plant immune responses by a central circadian regulator. Nature 470, 110–114 (2011).

  87. 87.

    Du, L. Y. et al. The innate immune cell response to bacterial infection in larval zebrafish is light-regulated. Sci. Rep. 7, 12657 (2017).

  88. 88.

    Lazado, C. C., Skov, P. V. & Pedersen, P. B. Innate immune defenses exhibit circadian rhythmicity and differential temporal sensitivity to a bacterial endotoxin in Nile tilapia (Oreochromis niloticus). Fish Shellfish Immunol. 55, 613–622 (2016).

  89. 89.

    Prendergast, B. J. et al. Circadian disruption alters the effects of lipopolysaccharide treatment on circadian and ultradian locomotor activity and body temperature rhythms of female Siberian hamsters. J. Biol. Rhythms 30, 543–556 (2015).

  90. 90.

    Johnson, C. H., Elliott, J., Foster, R., Honma, K. & Kronauer, R. Chronobiology: Biological Timekeeping (Sinauer Associates, 2004).

  91. 91.

    Michael, T. P. et al. Enhanced fitness conferred by naturally occurring variation in the circadian clock. Science 302, 1049–1053 (2003).

  92. 92.

    Dodd, A. N. et al. Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage. Science 309, 630–633 (2005).

  93. 93.

    Stephan, F. K. The “other” circadian system: food as a zeitgeber. J. Biol. Rhythms 17, 284–292 (2002).

  94. 94.

    Young, M. W. & Kay, S. A. Time zones: a comparative genetics of circadian clocks. Nat. Rev. Genet. 2, 702–715 (2001).

  95. 95.

    Dunlap, J. C. Molecular bases for circadian clocks. Cell 96, 271–290 (1999).

  96. 96.

    Chen, Z., Odstrcil, E. A., Tu, B. P. & McKnight, S. L. Restriction of DNA replication to the reductive phase of the metabolic cycle protects genome integrity. Science 316, 1916–1919 (2007).

  97. 97.

    Ouyang, Y., Andersson, C. R., Kondo, T., Golden, S. S. & Johnson, C. H. Resonating circadian clocks enhance fitness in cyanobacteria. Proc. Natl Acad. Sci. USA 95, 8660–8664 (1998).

  98. 98.

    Nelson, B. V. & Vance, R. R. Diel foraging patterns of the sea urchin Centrostephanus coronatus as a predator avoidance strategy. Mar. Biol. 51, 251–258 (1979).

  99. 99.

    Hughes, D. P. et al. Behavioral mechanisms and morphological symptoms of zombie ants dying from fungal infection. BMC Ecol. 11, 13 (2011).

  100. 100.

    de Bekker, C., Ohm, R. A., Evans, H. C., Brachmann, A. & Hughes, D. P. Ant-infecting Ophiocordyceps genomes reveal a high diversity of potential behavioral manipulation genes and a possible major role for enterotoxins. Sci. Rep. 7, 12508 (2017).

  101. 101.

    Fredericksen, M. A. et al. Three-dimensional visualization and a deep-learning model reveal complex fungal parasite networks in behaviorally manipulated ants. Proc. Natl Acad. Sci. USA 114, 12590–12595 (2017).

  102. 102.

    Garcia, C. R. S., Markus, R. P. & Madeira, L. Tertian and quartan fevers: temporal regulation in malarial infection. J. Biol. Rhythms 16, 436–443 (2001).

  103. 103.

    O’Donnell, A. J., Schneider, P., McWatters, H. G. & Reece, S. E. Fitness costs of disrupting circadian rhythms in malaria parasites. Proc. Biol. Sci. 278, 2429–2436 (2011).

  104. 104.

    Rund, S. S. C., Hou, T. Y., Ward, S. M., Collins, F. H. & Duffield, G. E. Genome-wide profiling of diel and circadian gene expression in the malaria vector. Proc. Natl Acad. Sci. USA 108, E421–E430 (2011).

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Acknowledgements

We thank the Darwin Trust of Edinburgh (M.L.W.), the National Science Foundation (M.Z.), NERC and BBSRC (NE/K006029/1; S.E.R.), the Royal Society (UF110155; S.E.R.), and the Wellcome Trust (202769/Z/16/Z; S.E.R.) for supporting this work.

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S.E.R. conceived the study, M.L.W. and S.E.R. drafted the manuscript, and all authors provided substantial input into ideas and the writing of subsequent drafts.

Correspondence to Mary L. Westwood.

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