Abstract
The circadian clock, which evolved to help organisms harmonize physiological responses to external conditions (such as the light/dark cycle, LD), is emerging as an important regulator of the immune response to infection. Gaining a complete understanding of how the circadian clock influences the immune cell response requires animal models that permit direct observation of these processes within an intact host. Here, we investigated the use of larval zebrafish, a powerful live imaging system, as a new model to study the impact of a fundamental zeitgeber, light, on the innate immune cell response to infection. Larvae infected during the light phase of the LD cycle and in constant light condition (LL) demonstrated enhanced survival and bacterial clearance when compared with larvae infected during the dark phase of the LD cycle and in constant dark condition (DD). This increased survival was associated with elevated expression of the zebrafish orthologues of the mammalian pro-inflammatory cytokine genes, Tumour necrosis factor-α, Interleukin-8 and Interferon-γ, and increased neutrophil and macrophage recruitment. This study demonstrates for the first time that the larval zebrafish innate immune response to infection is enhanced during light exposure, suggesting that, similar to mammalian systems, the larval zebrafish response to infection is light-regulated.
Highlights
Organisms encounter higher risks to infection at certain times of the day
We investigated whether the innate immune response to infection in larval zebrafish is influenced by light
We investigated per2a and aanat[2] expression by whole mount in situ hybridization (WMISH) analysis under the following light conditions: 14-hour light/10-hour dark cycle (LD), constant light (LL), reversed 14-hour light/10-hour dark cycle (DL) and constant darkness (DD) (Fig. 1a)
Summary
Organisms encounter higher risks to infection at certain times of the day. This timing is dependent on environmental conditions associated with increased virulence of pathogens and vulnerability of the host. Studies using this model have revealed rhythmicity in the phagocytic activity of leukocytes and migration of neutrophils and light-dependent changes in serum immune parameters[26,27,28] To date, it has not been reported whether the larval zebrafish innate immune cell response to infection is light - dependent. We show that the innate immune response to Salmonella enterica serovar Typhimurium (hereafter referred to as Salmonella) infection was enhanced during light exposure This is likely to be mediated by the greater expression of the pro-inflammatory cytokine genes, tumor necrosis factor a (tnf-a), chemokine (C-X-C motif) ligand 8a (cxcl8a) and interferon gamma 1-1 (ifng1-1), and the elevated recruitment of neutrophils and macrophages to the site of infection, suggesting that the innate immune response in larval zebrafish is light-regulated. The powerful experimental techniques available using this model will serve as a strong platform to uncover new mechanistic insights into how light influences the innate immune cell response during infection
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