The damage-response framework of microbial pathogenesis

Abstract

Existing definitions of microbial pathogenicity and virulence are inadequate to explain many infectious diseases and do not incorporate the contribution of the host to these processes. A new theoretical approach to understanding microbial pathogenesis — the damage-response framework – is proposed. The damage-response framework differs from other views of microbial pathogenesis as it is neither microorganism-centred nor host-centred. Instead, the damage-response framework is based on the fact that microbial pathogenesis is the outcome of an interaction between a host and a microorganism, and uses host damage as a common principle that incorporates the role of both the host and the microorganism. The host-immune response can augment or delimit the nature and amount of host damage resulting from a host–microorganism interaction. Therefore, in the damage-response framework, pathogens are classified by the amount, or degree, of host damage that results from host–microorganism interactions as a function of the host-immune response. Six different classes are proposed, and are depicted in parabolic damage-response curves that represent the amount of host damage as a function of the intensity and degree of the host response. The amount or degree of host damage that results from the host–microorganism interaction as a function of time can be used to define and characterize the outcome of infection as the states of commensalism, colonization, latency or disease. The damage-response framework is based on clinical and experimental observations of the outcome of host–microorganism interactions. Its associated classifications and predictions can be subjected to further experimental studies to validate or refute its ability to account for the contributions of both host and microorganism to microbial pathogenesis. The damage-response framework of microbial pathogenesis could assist in the design of vaccines and immunotherapies and in the characterization of new infectious diseases. Its simplified classification system is a useful educational tool. Additionally, use of the damage-response framework could foster collaboration between investigators in different, and at present separate, areas of microbial pathogenesis research.