4.4 Article

Vitamin D Enhances Neutrophil Generation and Function in Zebrafish (Danio rerio)

Journal

JOURNAL OF INNATE IMMUNITY
Volume 14, Issue 3, Pages 229-242

Publisher

KARGER
DOI: 10.1159/000519183

Keywords

Vitamin D-3; Granulopoiesis; Microbiota; Neutrophil recruitment; Infection

Categories

Funding

  1. National Natural Science Foundation of China [31972802]
  2. Natural Science Foundation of Shandong Province [ZR2019MC041]
  3. National Key R&D Program of China [2018YFD0900400]
  4. Laboratory for Marine Fisheries Science and Food Production Processes, Pilot National Laboratory for Marine Science Technology (Qingdao) [2018-MFS-T11]
  5. Fundamental Research Funds for the Central Universities [201961025]

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Vitamin D has a significant impact on the generation and function of neutrophils in zebrafish, promoting granulopoiesis and enhancing neutrophil activity. VD also reduces bacterial counts and mortality in zebrafish infected with pathogens, in a neutrophil-dependent manner.
Vitamin D (VD) is a major regulator of calcium metabolism in many living organisms. In addition, VD plays a key role in regulating innate and adaptive immunity in vertebrates. Neutrophils constitute an important part of the first line of defense against invading microbes; however, the potential effect of VD on neutrophils remains elusive. Thus, in this study zebrafish in different developmental stages were utilized to identify the potential role of VD in the basal homeostasis and functions of neutrophils. Our results showed that addition of exogenous VD3 promoted granulopoiesis in zebrafish larvae. Reciprocally, neutrophil abundance in the intestine of adult zebrafish with a cyp2r1 mutant, lacking the capacity to 25-hydroxylate VD, was reduced. Moreover, VD-mediated granulopoiesis was still observed in gnotobiotic zebrafish larvae, indicating that VD regulates neutrophil generation independent of the microbiota during early development. In contrast, VD was incapable to influence granulopoiesis in adult zebrafish when the commensal bacteria were depleted by antibiotic treatment, suggesting that VD might modulate neutrophil activity via different mechanisms depending on the developmental stage. In addition, we found that VD3 augmented the expression of il-8 and neutrophil recruitment to the site of caudal fin amputation. Finally, VD3 treatment significantly decreased bacterial counts and mortality in zebrafish infected with Edwardsiella tarda (E. tarda) in a neutrophil-dependent manner. Combined, these findings demonstrate that VD regulates granulopoiesis and neutrophil function in zebrafish immunity.

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