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A Three-Tiered Study of Differences in Murine Intrahost Immune Response to Multiple Pneumococcal Strains.

Mochan-Keef E, Swigon D, Ermentrout GB, Clermont G - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Joint Carnegie Mellon University-University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, PA, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus

Analysis of bacteria-dependent parameters in the pneumolysin activity study.(A) One-dimensional parameter distributions of bacteria-dependent parameters: h, q, ν, ξnl, ξnb. The top row (green) shows ensembles for H+/C- bacteria. The middle row (red) shows ensembles for H2-/C+ bacteria. The bottom row (blue) shows ensembles for wild-type (WT) bacteria. (B) Principal values computed from singular-value decomposition of ensembles for each bacterial strain. (C-E) Two-dimensional parameter correlations for H+/C- (C) H2-/C+ (D) and wild-type (E) bacteria.
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pone.0134012.g002: Analysis of bacteria-dependent parameters in the pneumolysin activity study.(A) One-dimensional parameter distributions of bacteria-dependent parameters: h, q, ν, ξnl, ξnb. The top row (green) shows ensembles for H+/C- bacteria. The middle row (red) shows ensembles for H2-/C+ bacteria. The bottom row (blue) shows ensembles for wild-type (WT) bacteria. (B) Principal values computed from singular-value decomposition of ensembles for each bacterial strain. (C-E) Two-dimensional parameter correlations for H+/C- (C) H2-/C+ (D) and wild-type (E) bacteria.

Mentions: We next explore differences in the posterior distributions of the bacteria-strain-dependent parameters (Fig 2A). H+/C- bacteria distributions (Fig 2A, top row) show a bimodal response of the phagocytes, and the pairwise parameter correlations in Fig 2C indicate these parameters are inversely correlated. Thus, when lung phagocytosis rates (ξnl) are high, blood phagocytosis (ξnb) tends to be less effective, and vice versa. Since this strain lacks complement activation, we would expect a generally low level of phagocytic activity. Interestingly, even though this strain has full hemolytic activity, the distribution of the damage production rate q exists in the lower half of its bounds. This likely occurs because lung bacteria levels remain high throughout the full course of the infection, and thus the values for q do not need to be exceedingly high in order to produce movement into the blood compartment.


A Three-Tiered Study of Differences in Murine Intrahost Immune Response to Multiple Pneumococcal Strains.

Mochan-Keef E, Swigon D, Ermentrout GB, Clermont G - PLoS ONE (2015)

Analysis of bacteria-dependent parameters in the pneumolysin activity study.(A) One-dimensional parameter distributions of bacteria-dependent parameters: h, q, ν, ξnl, ξnb. The top row (green) shows ensembles for H+/C- bacteria. The middle row (red) shows ensembles for H2-/C+ bacteria. The bottom row (blue) shows ensembles for wild-type (WT) bacteria. (B) Principal values computed from singular-value decomposition of ensembles for each bacterial strain. (C-E) Two-dimensional parameter correlations for H+/C- (C) H2-/C+ (D) and wild-type (E) bacteria.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526468&req=5

pone.0134012.g002: Analysis of bacteria-dependent parameters in the pneumolysin activity study.(A) One-dimensional parameter distributions of bacteria-dependent parameters: h, q, ν, ξnl, ξnb. The top row (green) shows ensembles for H+/C- bacteria. The middle row (red) shows ensembles for H2-/C+ bacteria. The bottom row (blue) shows ensembles for wild-type (WT) bacteria. (B) Principal values computed from singular-value decomposition of ensembles for each bacterial strain. (C-E) Two-dimensional parameter correlations for H+/C- (C) H2-/C+ (D) and wild-type (E) bacteria.
Mentions: We next explore differences in the posterior distributions of the bacteria-strain-dependent parameters (Fig 2A). H+/C- bacteria distributions (Fig 2A, top row) show a bimodal response of the phagocytes, and the pairwise parameter correlations in Fig 2C indicate these parameters are inversely correlated. Thus, when lung phagocytosis rates (ξnl) are high, blood phagocytosis (ξnb) tends to be less effective, and vice versa. Since this strain lacks complement activation, we would expect a generally low level of phagocytic activity. Interestingly, even though this strain has full hemolytic activity, the distribution of the damage production rate q exists in the lower half of its bounds. This likely occurs because lung bacteria levels remain high throughout the full course of the infection, and thus the values for q do not need to be exceedingly high in order to produce movement into the blood compartment.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Joint Carnegie Mellon University-University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, PA, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus