The mice were also weighed daily to monitor illness, as defined by percent weight loss ( 0.01). Pathological results were in accordance with the findings described earlier. prevented excess weight loss, resulted in a significant reduction in pulmonary computer virus titers, Schizandrin A and largely reduced virus-induced lung pathology. Thus, this study reveals an intracellular mechanism for viral neutralization in polarized epithelial cells that is dependent on FcRn-mediated transport of neutralizing IgG. 0.05 and ** 0.01. To further test whether the intracellular neutralization of influenza computer virus by Y8 mAb in MDCK-FcRn cells was dependent on FcRn-mediated RGS19 IgG transcytosis, we performed two experiments. First, we used MDCK cells expressing a chimeric FcRn and GFP, which is unable to transcytose IgG (5), and we verified this result (Fig. S4and 0.01 and *** 0.001. To further investigate the fate of computer virus particles, antiClysosome-associated membrane glycoprotein-2 (LAMP-2), a lysosomal marker, and anti-NP mAbs were used to follow virion trafficking to nuclear or lysosomal sites. Transport of the computer virus particles to the lysosomes was negligible in control IgG-treated MDCK-FcRn cells during the incubation periods indicated (Fig. 3 0.05). The majority of animals Schizandrin A that received irrelevant IgG or PBS answer died of contamination within 6 d after challenge. Therefore, the administration of Y8 mAb in the WT mice was clearly associated with a survival benefit compared with control animals. Even though FcRn-KO mice receiving the Y8 mAb showed a pattern toward increased survival, the increase was not significantly different from control animals. In addition, WT animals treated with Y8 mAb did not significantly drop body weight, whereas the mean excess weight loss in the control group was approximately 30% by the time the mice died or were Schizandrin A euthanized ( 0.01). FcRn-KO mice that received Y8 Schizandrin A mAb showed similar decreases in body weight as the control animals, with a 25% imply weight loss (Fig. 4 0.01). Open in a separate windows Fig. 4. PR8 HA-specific Y8 mAb guarded mice from computer virus contamination. (and = 15). The mice were also weighed daily to monitor illness, as defined by percent excess weight loss ( 0.01). Pathological results were in accordance with the findings explained earlier. No lesions were present in the lungs of mock-infected mice (Fig. 5provides further details. Supplementary Material Supporting Information: Click here to view. Acknowledgments We thank Geoffrey J. Letchworth for crucial reading of the manuscript, Peter Palese for the influenza PR8 strain, and Keith Mostov for the MadinCDarby canine kidney type II cell collection; Neil Simister for helpful discussions of mouse IgG catabolism; and Senthilkumar Palaniyandi, Rongyu Zeng, Xindong Liu, Zili Li, and Yunsheng Wang for technical help. This work was supported in part by National Institutes of Health Grants AI65892 (to X.Z.), AI67965 (to X.Z.), AI73139 (to X.Z.), DK56597 (to D.C.R.), and R37 AI041239-06A1 (to P.J.B.). Footnotes The authors declare no discord of interest. This short article is usually a PNAS Direct Submission. This short article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1115348108/-/DCSupplemental..