Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/28710
Title: Genetic factors regulating lung vasculature and immune cell functions associate with resistance to pneumococcal infection
Authors: Jonczyk, Magda S.
Simon, Michelle
Kumar, Saumya
Fernandes, Vitor E.
Sylvius, Nicolas
Mallon, Ann-Marie
Denny, Paul
Andrew, Peter W.
First Published: 3-Mar-2014
Publisher: Public Library of Science
Citation: PLoS ONE, 2014, 9 (3), e89831
Abstract: Streptococcus pneumoniae is an important human pathogen responsible for high mortality and morbidity worldwide. The susceptibility to pneumococcal infections is controlled by as yet unknown genetic factors. To elucidate these factors could help to develop new medical treatments and tools to identify those most at risk. In recent years genome wide association studies (GWAS) in mice and humans have proved successful in identification of causal genes involved in many complex diseases for example diabetes, systemic lupus or cholesterol metabolism. In this study a GWAS approach was used to map genetic loci associated with susceptibility to pneumococcal infection in 26 inbred mouse strains. As a result four candidate QTLs were identified on chromosomes 7, 13, 18 and 19. Interestingly, the QTL on chromosome 7 was located within S. pneumoniae resistance QTL (Spir1) identified previously in a linkage study of BALB/cOlaHsd and CBA/CaOlaHsd F2 intercrosses. We showed that only a limited number of genes encoded within the QTLs carried phenotype-associated polymorphisms (22 genes out of several hundred located within the QTLs). These candidate genes are known to regulate TGFb signalling, smooth muscle and immune cells functions. Interestingly, our pulmonary histopathology and gene expression data demonstrated, lung vasculature plays an important role in resistance to pneumococcal infection. Therefore we concluded that the cumulative effect of these candidate genes on vasculature and immune cells functions as contributory factors in the observed differences in susceptibility to pneumococcal infection. We also propose that TGFbmediated regulation of fibroblast differentiation plays an important role in development of invasive pneumococcal disease.
DOI Link: 10.1371/journal.pone.0089831
ISSN: 1932-6203
Links: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0089831
http://hdl.handle.net/2381/28710
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2014 Jonczyk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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