Biofilm neutrophils interactions under hypoxia: A mathematical modeling study

Neutrophils are important to the defense of the host against bacterial infection. Pathogens and the immune system cells create via respiration, a hypoxic environment in infected regions. Hypoxic conditions affect both the neutrophil's ability to eradicate the infection and also change the behavior of the bacterial-pathogens by eliciting the production of various virulence factors, the creation of bacterial biofilm and the initialization of anaerobic metabolism. In this work interactions of bacterial biofilm and neutrophils are studied in a domain where oxygen is diffusing into the environment and is being consumed by biofilm. Within a hypoxic environment, bacteria grow anaerobically and secrete higher levels of toxin that diffuses and lyses neutrophils. A mathematical model explicitly representing the biofilm volume fraction, oxygen, and diffusive virulence factors (toxin) as well as killing of bacteria by neutrophils is developed and studied first in 1D and then in 2D. Stability analysis and numerical simulations showing the effects of oxygen and toxin concentration on neutrophil-bacteria interactions are presented to identify different possible scenarios that can lead to elimination of the infection or its persistence as a chronic infection. Specifically, when bacteria are allowed to utilize anaerobic breathing and or to produce toxin, their fitness is enhanced against neutrophils attacks. A possible insight on how virulent bacterial colonies can synergistically resist neutrophils and survive is presented.