Disentangling the interaction among host resources, the immune system and pathogens

Abstract

The interaction between the immune system and pathogens is often characterised as a predator-prey interaction. This characterisation ignores the fact that both require host resources to reproduce. Here, we propose novel theory that considers how these resource requirements can modify the interaction between the immune system and pathogens. We derive a series of models to describe the energetic interaction between the immune system and pathogens, from fully independent resources to direct competition for the same resource. We show that increasing within-host resource supply has qualitatively distinct effects under these different scenarios. In particular, we show the conditions for which pathogen load is expected to increase, decrease or even peak at intermediate resource supply. We survey the empirical literature and find evidence for all three patterns. These patterns are not explained by previous theory, suggesting that competition for host resources can have a strong influence on the outcome of disease.

Keywords: Consumer-resource theory; epidemiology; immunology; modelling.

Figure 1

Depiction of the possible topologies of the interaction between energy E, the immune system I and pathogens N. Energy from the reserves can be used directly to fuel immune proliferation or pathogen replication, or it can first be allocated to intermediate energy bins E_I and E_N that fuel proliferation and replication.

Figure 2

Equilibrium model predictions as energy acquisition rate θ increases. Panels a–d show the equilibrium abundances (solid), (dashed) and (dot-dash). The proximate resource for the immune system is highlighted in dark grey and the proximate resource for the pathogen is highlighted in light grey. Panels e–h show the immune abundances when the pathogen is present (solid, N+) and absent (dashed, N−). Note that increasing energy acquisition increases the number of immune cells even in the absence of infection because of the baseline immune allocation parameter a_B. Panels i–l show the pathogen load. Panels m–p show the net gain rate (solid, point-up triangles) and per capita loss rate (dashed, point-down triangles) of the pathogen's resource (the numerator and denominator, respectively, of the equations in Table2). Note that these quantities have different units (1/time vs. 1/pathogens/time). Parameter values are given in Table1.

Figure 3

The regions of parameter space where increasing energy acquisition rate θ increases pathogen load for the immune priority and energy antagonism models. The solid line in all four panels shows the θ values where pathogen load peaks. Panels a and b show this peak for varying values of pathogen energy consumption rate f_N, whereas panels c and d show the peak for varying values of immune killing rate f_I. For parameter combinations in the hatched regions, increasing θ increases pathogen load.

Figure 4

The number of host–pathogen systems showing an increase, decrease or intermediate peak in pathogen abundance as host food is increased, when the host is a bacteria, invertebrate or vertebrate. All three model-predicted responses can be found in the empirical literature.