title: A Three-Tiered Study of Differences in Murine Intrahost Immune Response to Multiple Pneumococcal Strains.
abstract: 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.
authors.affiliation: Joint Carnegie Mellon University-University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, PA, United States of America.
authors.forename: Ericka
authors.initials: E
authors.lastname: Mochan-Keef
authors.affiliation: Department of Mathematics, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Swigon
authors.affiliation: Department of Mathematics, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: G Bard
authors.initials: GB
authors.lastname: Ermentrout
authors.affiliation: Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America; McGowan Institute for Regenerative Medicine, Center for Inflammation and Regenerative Modeling, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors.forename: Gilles
authors.initials: G
authors.lastname: Clermont
mesh_terms: D000465:Algorithms; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018448:Models, Immunological; D009439:Neuraminidase / Q000276:immunology / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology; D012703:Serotyping; D013045:Species Specificity; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology* / Q000502:physiology; D013301:Streptolysins / Q000276:immunology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D007527:Isoenzymes; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D009439:Neuraminidase