Multiscale modeling of host-pathogen interactions and mucociliary clearance during non-tuberculous mycobacterial pulmonary infection
Abstract
Non-tuberculous mycobacterial (NTM) infections are a clinical challenge in cystic fibrosis (CF), where impaired mucociliary clearance and altered mucus rheology promote bacterial colonization despite host immune responses. Understanding how bacterial growth, immune cell dynamics, and mucus transport regulate infection progression is difficult because these processes interact across spatial and temporal scales. We develop a computational framework bridging a mechanistic agent-based model (ABM) of NTM infection with a spatially resolved partial differential equation (PDE) model. The PDE model couples bacterial proliferation, macrophage chemotaxis, immune-mediated clearance, mucus degradation, and viscoelastic transport in a two-compartment geometry representing mucus and lung tissue. Parameters are calibrated using data from the established ABM, yielding an efficient continuum representation while preserving cellular mechanisms. The PDE model reproduces bacterial and macrophage dynamics and enables analyses of mucus-related mechanisms and therapies. Sensitivity analysis identifies mucus viscosity, bacterial diffusivity, and macrophage mobility as key regulators of bacterial persistence through mucociliary clearance and tissue colonization. Simulations reveal nonlinear effects of mucolytic therapies: enhanced clearance reduces bacterial burden in mucus, whereas excessive viscosity reduction may promote migration into lung tissue, supporting combination with antibacterial treatment. This framework provides a quantitative platform for studying pulmonary infections, evaluating therapies, and developing patient-specific digital twins.
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BibTeX
@misc{wang2026multiscale,
title = {{Multiscale modeling of host-pathogen interactions and mucociliary clearance during non-tuberculous mycobacterial pulmonary infection}},
author = {Jindong Wang and Kali Konstantinopoulos and Po-Chun Kuo and Mingchao Cai and Ning Wei and Elsje Pienaar and Wenrui Hao},
howpublished = {arXiv},
year = {2026},
month = sep,
doi = {10.48550/arxiv.2609.15584},
eprint = {2609.15584},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2609.15584},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Multiscale modeling of host-pathogen interactions and mucociliary clearance during non-tuberculous mycobacterial pulmonary infection
AU - Jindong Wang
AU - Kali Konstantinopoulos
AU - Po-Chun Kuo
AU - Mingchao Cai
AU - Ning Wei
AU - Elsje Pienaar
AU - Wenrui Hao
PY - 2026
DA - 2026/09/14
PB - arXiv
DO - 10.48550/arxiv.2609.15584
UR - https://arxiv.org/abs/2609.15584
AB - Non-tuberculous mycobacterial (NTM) infections are a clinical challenge in cystic fibrosis (CF), where impaired mucociliary clearance and altered mucus rheology promote bacterial colonization despite host immune responses. Understanding how bacterial growth, immune cell dynamics, and mucus transport regulate infection progression is difficult because these processes interact across spatial and temporal scales. We develop a computational framework bridging a mechanistic agent-based model (ABM) of NTM infection with a spatially resolved partial differential equation (PDE) model. The PDE model couples bacterial proliferation, macrophage chemotaxis, immune-mediated clearance, mucus degradation, and viscoelastic transport in a two-compartment geometry representing mucus and lung tissue. Parameters are calibrated using data from the established ABM, yielding an efficient continuum representation while preserving cellular mechanisms. The PDE model reproduces bacterial and macrophage dynamics and enables analyses of mucus-related mechanisms and therapies. Sensitivity analysis identifies mucus viscosity, bacterial diffusivity, and macrophage mobility as key regulators of bacterial persistence through mucociliary clearance and tissue colonization. Simulations reveal nonlinear effects of mucolytic therapies: enhanced clearance reduces bacterial burden in mucus, whereas excessive viscosity reduction may promote migration into lung tissue, supporting combination with antibacterial treatment. This framework provides a quantitative platform for studying pulmonary infections, evaluating therapies, and developing patient-specific digital twins.
ER -