Transcriptional events during the recovery from MRSA lung infection: a mouse pneumonia model.
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.
Department of Medicine, Northwestern University, Chicago, Illinois, USA. chenjw@uic.edu
Jiwang
J
Chen
Gang
G
Feng
Qiang
Q
Guo
Juliane B
JB
Wardenburg
Simon
S
Lin
Ichiro
I
Inoshima
Ryan
R
Deaton
Jason X J
JX
Yuan
Joe G N
JG
Garcia
Roberto F
RF
Machado
Michael
M
Otto
Richard G
RG
Wunderink
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002452:Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D004195:Disease Models, Animal; D023281:Genomics; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability; D011014:Pneumonia / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D015203:Reproducibility of Results; D013997:Time Factors; D014158:Transcription, Genetic; D059467:Transcriptome