Hif-1α stabilisation reduces bacterial burden in zebrafish embryos.

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Hif-1α stabilisation reduces bacterial burden in zebrafish embryos. Hif-1α stabilisation reduces bacterial burden in zebrafish embryos. (A) Zebrafish embryos were infected with Mycobacterium marinum (red) at 1 day postfertilisation by injection into the caudal vein. By 4 days postinfection, foci of M. marinum (red) are surrounded by infected and uninfected leukocytes (green; L-plastin antibody staining) in structures known as granulomas. (B) Stabilisation of Hif-1α, using dominant active (DA) Hif-1αb reduces the bacterial burden of zebrafish embryos compared with phenol red (PR)-injected controls. However, when macrophage numbers are depleted using an antisense oligonucleotide morpholino to the crucial macrophage transcription factor irf-8 (Li et al., 2011), bacteria are able to proliferate in an uncontrolled manner and dominant active Hif-1αb stabilisation is powerless to decrease infection. Neutrophils, marked in green (using the Tg(mpx:GFP)i114 transgenic zebrafish line; Renshaw et al., 2006), have emerging roles in granuloma formation and maintenance, but without macrophages present they cannot control infection alone. Images are from P.M.E. and A.H.M., unpublished observations. Philip M. Elks et al. Dis. Model. Mech. 2015;8:1349-1360 © 2015. Published by The Company of Biologists Ltd