VIPhyb, an Antagonist of Vasoactive Intestinal Peptide Receptor, Enhances Cellular Antiviral Immunity in Murine Cytomegalovirus Infected Mice
Figure 3
Blocking VIP-signaling decreased inflammation and necrosis in the liver and lung of mCMV-infected mice.
VIP-KO and WT littermate C57BL/6 mice treated with 7 daily subcutaneous doses of VIPhyb (starting one day before mCMV infection) or WT littermate with PBS were infected i.p. with 1×105 PFU mCMV. Four mice were euthanized each time-point at 3, 7 and 10 days following mCMV infection. The livers and the lungs were processed for histological analysis. The number of intra-nuclear inclusions (at 20×magnification), numbers of infiltrated nucleated cells, and numbers necrotic foci (at 10×magnification, moderate: necrosis with equal or less than 10 infiltrated nucleated cells, severe: necrosis with more than 10 infiltrated nucleated cells) were determined from hematoxylin and eosin-stained paraffin sections. Data are averaged from 10 random representative area of 0.26 mM2 from 2 sections per mouse and per time-point. Data (mean ± SD) are shown from 4 mice per time-point and per group. A: Liver and lung pathology 3,7, and 10 days following mCMV infection. Graphs are shown in 20×magnification with 60×magnification insert. Scale bar (yellow line) is 20 µM. Arrowhead points to necrotic focus; arrow points to intra-nuclear inclusions. B: Number of intra-nuclear inclusions in the liver 3 days following mCMV infection. C: Necrotic foci in the liver 3 days following mCMV infection. D: Infiltrating leukocytes in the liver following mCMV infection. E. Infiltrating leukocytes in the lung following mCMV infection. *p<0.05, **p<0.01, and ***p<0.001 denote significant differences between VIP-KO mice or VIPhyb-treated mice vs. PBS-treated WT mice.