journal.pone.0070176.pdf (1.02 MB)
Transcriptional Events during the Recovery from MRSA Lung Infection: A Mouse Pneumonia Model
journal contributionposted on 2013-10-22, 00:00 authored by Jiwang Chen, Gang Feng, Qiang Guo, Juliane B. Wardenburg, Simon Lin, Ichiro Inoshima, Ryan Deaton, Jason X. J. Yuan, Joe G. N. Garcia, Roberto F. Machado, Michael Otto, Richard G. Wunderink
Community associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging threat to human health throughout the world. Rodent MRSA pneumonia models mainly focus on the early innate immune responses to MRSA lung infection. However, the molecular pattern and mechanisms of recovery from MRSA lung infection are largely unknown. In this study, a sublethal mouse MRSA pneumonia model was employed to investigate late events during the recovery from MRSA lung infection. We compared lung bacterial clearance, bronchoalveolar lavage fluid (BALF) characterization, lung histology, lung cell proliferation, lung vascular permeability and lung gene expression profiling between days 1 and 3 post MRSA lung infection. Compared to day 1 post infection, bacterial colony counts, BALF total cell number and BALF protein concentration significantly decreased at day 3 post infection. Lung cDNA microarray analysis identified 47 significantly up-regulated and 35 down-regulated genes (p<0.01, 1.5 fold change [up and down]). The pattern of gene expression suggests that lung recovery is characterized by enhanced cell division, vascularization, wound healing and adjustment of host adaptive immune responses. Proliferation assay by PCNA staining further confirmed that at day 3 lungs have significantly higher cell proliferation than at day 1. Furthermore, at day 3 lungs displayed significantly lower levels of vascular permeability to albumin, compared to day 1. Collectively, this data helps us elucidate the molecular mechanisms of the recovery after MRSA lung infection.
This study was supported by Pfizer ASPIRE Award, Pfizer Investigator-Initiated Grant (WS1826185, to Chen), the National Center for Advancing Translational Sciences Grant (8UL1TR000150) and the NCI Cancer Center Support Grant (NCI CA060553 to Feng and Lin) and the Intramural Research Program of the NIAID (to Otto)
Publisher Statement© 2013 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This is a copy of an article published in the PLoS ONE © 2013 Public Library of Science
PublisherPublic Library of Science