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A three-tiered study of differences in murine intrahost immune response to multiple pneumococcal strains

Mochan-Keef, E and Swigon, D and Ermentrout, GB and Clermont, G (2015) A three-tiered study of differences in murine intrahost immune response to multiple pneumococcal strains. PLoS ONE, 10 (8).

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© 2015 Mochan-Keef 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. We apply a previously developed 4-variable ordinary differential equation model of in-host immune response to pneumococcal pneumonia to study the variability of the immune response of MF1 mice and to explore bacteria-driven differences in disease progression and outcome. In particular, we study the immune response to D39 strain of bacteria missing portions of the pneumolysin protein controlling either the hemolytic activity or complement-activating activity, the response to D39 bacteria deficient in either neuraminidase A or B, and the differences in the response to D39 (serotype 2), 0100993 (serotype 3), and TIGR4 (serotype 4) bacteria. The model accurately reproduces infection kinetics in all cases and provides information about which mechanisms in the immune response have the greatest effect in each case. Results suggest that differences in the ability of bacteria to defeat immune response are primarily due to the ability of the bacteria to elude nonspecific clearance in the lung tissue as well as the ability to create damage to the lung epithelium.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Mochan-Keef, E
Swigon, Dswigon@pitt.eduSWIGON
Ermentrout, GB
Clermont, Gcler@pitt.eduCLER
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, or Units > McGowan Institute for Regenerative Medicine
Date: 5 August 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 10
Number: 8
DOI or Unique Handle: 10.1371/journal.pone.0134012
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Computational Biology
Dietrich School of Arts and Sciences > Mathematics
School of Medicine > Critical Care Medicine
Refereed: Yes
Date Deposited: 23 Aug 2016 14:29
Last Modified: 02 Feb 2019 15:56


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