KLF4 upregulation is involved in alternative macrophage activation during secondary Echinococcus granulosus infection.

The objective of this study was to investigate macrophage polarization during the early stages of secondary Echinococcus granulosus sensu lato (E. granulosus s.l.) infection. We observed an early initial increase in inflammatory genes (peaking at 5-10 days) and a later rise in M (IL-4)-like genes (still rising by day 15). In addition, we showed that the induction of M (IL-4)-like genes was paralleled by an increase in expression of the transcription factor KLF4. Most of the changes observed in vivo were reproduced in vitro upon the culture of normal peritoneal macrophages with live E. granulosus s.l. protoscoleces (PSC), and that knockdown of KLF4 in this system attenuates M (IL-4) differentiation. Our results suggest that KLF4 pathway contributes to the differentiation of macrophages towards M (IL-4)-like phenotype during early stages of secondary E. granulosus s.l. infection.