A mathematical model of intrahost pneumococcal pneumonia infection dynamics in murine strains

Abstract

The seriousness of pneumococcal pneumonia in mouse models has been shown to depend both on bacterial serotype and murine strain. We here present a simple ordinary differential equation model of the intrahost immune response to bacterial pneumonia that is capable of capturing diverse experimentally determined responses of various murine strains. We discuss the main causes of such differences while accounting for the uncertainty in the estimation of model parameters. We model the bacterial population in both the lungs and blood, the cellular death caused by the infection, and the activation and immigration of phagocytes to the infected tissue. The ensemble model suggests that inter-strain differences in response to streptococcus pneumonia inoculation reside in the strength of nonspecific immune response and the rate of extrapulmonary phagocytosis.

Host‐pathogen kinetics during influenza infection and coinfection: insights from predictive modeling

“…This model mimics infection data from a variety of conditions, including changes in bacterial dose, bacterial strain, murine strain, and under antibacterial therapy . The model accurately predicts that the ratio of aMΦs to bacteria regulates bacterial growth in the early stages of infection and that there is a critical threshold for which a clearance phenotype can be attained .…”

“…A thorough investigation into the uncertainty of the estimates and the corresponding model solution is also required. This has been particularly true when attempting to determine significant differences in parameter estimates generated by fitting a model to data obtained under varied experimental conditions, such as during infection with different virus strains, with different doses, in different host genetic backgrounds, or in different aged individuals . For this, ensemble‐style methods have been particularly useful.…”

“…For most bacterial infections, a simple model like the ones used for viruses cannot be used. This is because pneumococci are extracellular pathogens and their growth and clearance dynamics are highly dependent on interactions with host immune responses . Indeed, modeling pneumococcal dynamics required equations for several arms of the immune response to accurately capture bacterial kinetics from infections with varied initial doses .…”

“…Viral kinetics generally split into ~5 phases: initial infection of cells, exponential growth, peak, a slow decay, and a fast decay/clearance. Major host responses influencing these phases include, type I interferons (IFN), natural killer (NK) cells, T cells, and antibody (Ab) infection with different virus strains, 16,41 with different doses, 15,59 in different host genetic backgrounds, 60 or in different aged individuals. 59,61 For this, ensemble-style methods have been particularly useful.…”

Mechanism‐Based Disease Progression Model Describing Host‐Pathogen Interactions During the Pathogenesis of Acinetobacter baumannii Pneumonia

“…Mathematical modeling provides a means to incorporate and evaluate the impact of the immune response on the evolution and resolution of bacterial infection. Previous mathematical models of infection have explored the role of the immune response in infection . However, given the complexity of the immune response and the lack of measured immune components, these studies are largely theoretical in nature.…”