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IL-4/IL-13 polarization of macrophages enhances Ebola virus glycoprotein-dependent infection

Fig 7

Macrophage polarization increases morbidity and mortality in a mouse model.

A-C) Female Ifnar-/- mice were injected i.p. with 10ug IL-4/IL-13 or PBS 24 hours prior to i.p. infection with either 7x101 iu rVSV/EBOV GP (n = 10) or 1x102 iu rVSV/G (n = 5). Survival was monitored (A,B) or pmacs were isolated at day 2 post infection and assessed for viral load by qRT-PCR (C). D) Female Ifnar-/- (n = 12) or Ifnar/Timd-4-/- (n = 10) mice were infected i.p. with 104 iu of rVSV/EBOV GP and monitored daily for mortality. E). Male Ifnar/Timd-4-/- mice were injected i.p. with 10ug IL-4/IL-13 or PBS 24 hours prior to i.p. infection with 1x104 i.u. rVSV/EBOV GP. Survival was monitored (n = 8/group). F) Peritoneal macrophages from male Ifnar/Timd-4-/- mice were isolated and polarized to an M2a phenotype or treated with MCSF (controls) for 24 hours. Polarized cells were lifted and injected i.p. into recipient male Ifnar/Timd-4-/- mice (1.5x106 cells/mouse). Twenty-four hours after transfer of macrophages, mice were infected i.p. with 1x104 i.u. rVSV/EBOV GP and survival was monitored (n = 6/group). All in vivo experiments were performed a minimum of two times. Statistical analyses for all in vivo graphs were performed by Mantel-Cox test, p values indicated. For figure C statistics were performed by Student’s T-test, * indicates p<0.05.

Fig 7

doi: https://doi.org/10.1371/journal.pntd.0007819.g007