2. The host-pathogen interactome model
The use of immunomodulatory therapies to treat infectious disease, such
as the recent success of dexamethasone to treat COVID-19, is indicative
of the need to consider not only the disease-causing pathogen in
therapeutic development, but the contributions of the host too.
Casadevall and Pirofskiās seminal damage-response framework is based on
the fact that microbial pathogenesis, whether bacterial, fungal,
parasitic or viral is the outcome of interactions between the host and a
microorganism, and uses host damage as a common principle with which to
define and measure this interaction (Fig.1)12.
Although it may not always be possible to account for both views in
experimental design, conceptual consideration of the contributions of
both the host and the microorganism to host damage is important to focus
studies of microbial pathogenesis around a common principle, with the
potential to unify the field of microbial pathogenesis and allied
disciplines of immunology and vaccinology13-15.
Currently, classifications of microorganisms are based on phylogenetic
groups (bacteria, fungi, parasites, viruses)16,17.
Casadevall and Pirofski argue this system is limited by the fact that
most members of any group are not pathogenic in a host; of 150,000
fungal species, for example, only around 150 are pathogenic for
humans17. However, classifications based on the
perceived capacity of a microorganism to cause disease are equally
inadequate as changes in host immune function, ecology, and/or behaviour
can render them obsolete18. As discussed later,
classifying pathogens based on phylogenetic groups has been mirrored by
the antimicrobial lexicon, which currently classifies antimicrobials
according to their inhibitory activity against microbial phylogenetic
groups (antibiotics, antifungals, antiparasitics, antivirals),
encouraging a bias of therapeutic development towards pathogen-killing
as opposed to host-pathogen interactome targeting and
modulation19.
The use of host damage as the principle with which to categorise
pathogens allows them to be classified according to the common
denominator of pathogenic outcomes. Pathogens that cause similar types
of diseases can be grouped together despite differences in phylogeny and
growth characteristics. Pathogens grouped in a single class share
similarities with regard to the shape of the damage-response curve as a
function of the host immune response20,21. Ultimately,
the host-pathogen interactome model crystallises the contemporary view
of disease outcome as being determined both by the contributions of the
host as well as the pathogen, a marked departure from the classical
pathogen-centred view propounded in the early 20thcentury, with ramifications for microbial, immunological, and
antimicrobial studies.