In mammals, disrupted circadian rhythm is often correlated with infection and disease [1] and immunity can be specifically affected by circadian rhythm [2]. The molecular underpinnings of these interactions are unclear. Drosophila is a proven system for the study of both circadian rhythm [3] and innate immunity [4]. Microarray analyses of the fly have shown that the transcription of several immunity genes [5-8] is regulated in a circadian manner, but the significance of this regulation is not known.Here we demonstrate a functional, bidirectional relationship between circadian rhythm and innate immunity in Drosophila melanogaster. We show that fruit flies infected with the pathogenic bacteria Streptococcus pneumoniae or Listeria monocytogenes lose circadian regulation of locomotor activity several days before death and that circadian mutant flies (lacking either timeless or period, two central clock proteins in Drosophila) are highly sensitive to infection with these bacteria.
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