The trichotomy of pneumococcal infection outcomes

Abstract

AbstractThe successful elimination of bacteria such as Streptococcus pneumoniae from a host involves the coordination between different parts of the immune system. Previous studies have explored the effects of the initial pneumococcal load (bacterial dose) on different representations of innate immunity, finding that pathogenic outcomes can vary with the size of the bacterial dose. However, others yield support to the notion of dose-independent factors contributing to bacterial clearance. In this paper, we seek to provide a deeper understanding of the immune responses associated to the pneumococcus. To this end, we formulate a model that realizes an abstraction of the innate-regulatory immune host response. Stability and bifurcation analyses of the model reveal the following trichotomy of pneumococcal outcomes determined by the bifurcation parameters: (i) dose-independent clearance; (ii) dose-independent persistence; and (iii) dose-limited clearance. Bistability, where the bacteria-free equilibrium co-stabilizes with the most substantial steady-state bacterial load is the specific result behind dose-limited clearance. The trichotomy of pneumococcal outcomes here described integrates all previously observed bacterial fates into a unified framework.