Abstract
Bacterial infections occur when the natural host defenses are overwhelmed by invading bacteria. The main component of the host defense is impaired when neutrophil count or function is too low, putting the host at great risk of developing an acute infection. In people with intact immune systems, neutrophil count increases during bacterial infection. However, there are two important clinical cases in which they remain constant: a) in patients with neutropenic-associated conditions, such as those undergoing chemotherapy at the nadir (the minimum clinically observable neutrophil level); b) in ex vivo examination of the patient's neutrophil bactericidal activity. Here we study bacterial population dynamics under fixed neutrophil levels by mathematical modelling. We show that under reasonable biological assumptions, there are only two possible scenarios: 1) Bacterial behavior is monostable: it always converges to a stable equilibrium of bacterial concentration which only depends, in a gradual manner, on the neutrophil level (and not on the initial bacterial level). We call such a behavior type I dynamics. 2) The bacterial dynamics is bistable for some range of neutrophil levels. We call such a behavior type II dynamics. In the bistable case (type II), one equilibrium corresponds to a healthy state whereas the other corresponds to a fulminant bacterial infection. We demonstrate that published data of in vitro Staphylococcus epidermidis bactericidal experiments are inconsistent with both the type I dynamics and the commonly used linear model and are consistent with type II dynamics. We argue that type II dynamics is a plausible mechanism for the development of a fulminant infection.
Highlights
The human body is constantly exposed to bacterial influx from the environment via the skin, the respiratory tract and the digestive organs
For all levels of neutrophils there is a single stable equilibrium point (EP) which depends gradually on N : for low values it corresponds to the high concentration point associated with the maximal capacity branch–the branch of stable equilibria that emanates from the point ðN, BÞ~ð0, BÃÞ, where BÃ is the maximal capacity state of the natural bacterial dynamics
A model of bacterial dynamics interacting with a constant level of neutrophils and a constant influx term was constructed
Summary
The human body is constantly exposed to bacterial influx from the environment via the skin, the respiratory tract and the digestive organs. There are several known medically significant conditions of neutrophils with reduced number or function that are associated with an increased risk of infection: patients with severe neutropenia (neutrophil count less than 500|103 neutrophils/mL in the blood, which is three to ten times less than the normal values) [2,3]; people suffering from impaired microbicidal machinery (such as chronic granulomatous disease-CGD) [4,5]; individuals with neutrophiladhesion deficiency (which prevents the neutrophils from leaving the blood vessels and reaching the site of infection) [6]; individuals with insufficient vasculature to deliver neutrophils to the site of infection (e.g. deep burns) [7]. These observations motivated several groups to perform in-vitro experiments, with the notion that characterizing the bacterium-phagocyte dynamics would help decipher the in-vivo behavior of the innate immune system
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