Fig. 4

M1-like macrophages convert their phenotype toward M2-like phenotype in the wounded fin.

(A) Diagram showing the site where caudal fin was transected (dotted red line) in 3 dpf Tg(mpeg1:mCherryF/tnfa:eGFP-F) larvae. The black dotted box represents the region imaged by confocal microscopy. (B) Representative time-lapse maximum projections of 3 dpf Tg(mpeg1:mCherryF/tnfa:eGFP-F) amputated fins showing the fate of tnfa⁺ macrophages (magenta + green) at the indicated times pA (hours:minutes) from 6 hpA to 26 hpA. White lines delimit the caudal fin. Scale bar = 30 µm. (C) Tracking of tnfa⁺ macrophages from 6 to 26 hpA. The distinct colours of the lines correspond to the distinct macrophages that were indicated with an arrowhead in B. (D) Diagram representing macrophage activation and polarization in zebrafish. Unpolarized macrophages (mpeg1⁺) are mobilized and recruited to the wound following fin amputation. They are activated and polarized toward a M1-like phenotype (pro-inflammatory) few hours following fin amputation. After 24 hpA, in response to changes in environmental cues, the same macrophages progressively change their phenotype toward intermediate phenotypes and maybe fully polarized M2-like phenotype (non-inflammatory). Main markers of macrophage subtypes are indicated and resemble those found in human (tnfa/b indicates tumour necrosis factor alpha; il1b, interleukin 1-beta; il6, interleukin 6; tgfb1, tumour growth factor beta 1; ccr2, c–c chemokine receptor type 2; cxcr4b, chemokine (C-X-C motif) receptor 4b).