Fig 1.
Survival of larval Onchocerca volvulus in four mouse models.
O. volvulus L3 (100/mouse) were injected subcutaneously into 4 mouse models: (A,E) NSG mice (4 week n = 11 [2.3% Recovery], 8 week n = 4 [1.7% Recovery]), (B,F) Human skeletal muscle cell engrafted NSG mice (HuSkMc) (4 week n = 21 [3.0% Recovery], 8 week n = 12 [1.6% Recovery], 12 week n = 6 [1.8% Recovery]) (C,G) Humanized NSG (HuNSG) mice: NSG mice that received transfer of human CD34+ stem cells (4 week n = 16 [4.5% Recovery], 8 week n = 15 [4.6% Recovery]), (D,H) BLT mice: NSG mice engrafted with human fetal liver derived CD34+ stem cells and fetal thymus and liver tissues (4 week n = 9 [5.4% Recovery], 8 week n = 5 [2.3% Recovery]). After 4-, 8- or 12-weeks the percent established (the proportion of mice in a group of infected animals from which live parasites were recovered) (Fig 1A–1D) and the geometric mean number of live worms recovered per mouse within the group was determined (Fig 1E–1H).
Fig 2.
Growth of larval Onchocerca volvulus in four mouse models.
O. volvulus L3 (100/mouse) were injected subcutaneously into 4 different NSG based models: (1) NSG, (2) Human skeletal muscle cell engrafted NSG mice (HuSkMc), (3) Humanized NSG (HuNSG) mice: NSG mice that had received a human CD34+ stem cell transfer, (4) BLT: NSG mice that had been engrafted with human fetal liver derived CD34+ stem cells and engrafted with fetal thymus and liver tissues. After 4, 8 or 12-weeks, animals were necropsied and worms were recovered and measured. Solid colored bar is the geometric mean of the lengths of larvae recovered. Solid black line is the geometric mean of the length of L3 recovered from black flies and dotted line is the 95th confidence interval. *Asterisk represents statistical difference, p value ≤ 0.05, in length of larvae recovered from mice. Complete statistical analyses for all groups are included on S2 Table.
Fig 3.
Imaging of O. volvulus larvae recovered from various models.
A) Anterior end of female larva showing overall shape, location of nerve ring (small arrow) and vulva (large arrow). [Scale bar = 50 μm] B) Female tail, lateral view, showing overall shape and rectum (arrow heads) and anal opening (arrow). [Scale bar = 15 μm] C) Developing ovejector (arrowheads), lateral view, showing attachment to body wall and beginning of vulva (arrow). [Scale bar = 10 μm] D) Developing ovejector, dorsal-ventral view, showing the relative large cavity (asterisk) and the developing tube (arrows). [Scale bar = 10 μm] E) Male larva at approximately mid-body showing the testis (arrow), which is C-shaped, curved posteriorly, and has begun to grow posteriorly (arrowhead). [Scale bar = 10 μm] F) Male tail, lateral view showing overall shape. One developing spicule pad (arrowheads) is clearly visible as is the anal opening (arrow). [Scale bar = 15 μm].
Fig 4.
Proteomic identification in serum and urine of infected mice.
A) Proportional venn diagrams showing the distribution of O. volvulus-proteins in the serum and urine of BLT (8-weeks) and HuSkMc (12-weeks) mice infected with O. volvulus L3. B) Proteins identified commonly in serum and urine shown in A. The buttons indicate evidence of the protein as transcript only (red), protein only (blue) or both transcript and protein (purple), across the stages.