Review Article | Published:

The damage-response framework of microbial pathogenesis

Nature Reviews Microbiologyvolume 1pages1724 (2003) | Download Citation

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Abstract

The late twentieth century witnessed the emergence of numerous infectious diseases that are caused by microorganisms that rarely cause disease in normal, healthy immunocompetent hosts. The emergence of these diseases shows that the existing concepts of pathogenicity and virulence do not take into account the fact that both the microorganism and the host contribute to microbial pathogenesis. To address this impediment to studies of host–microorganism interactions, we propose a new theoretical approach to understanding microbial pathogenesis, known as the 'damage-response' framework.

Key Points

  • 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.

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References

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Affiliations

  1. Departments of Medicine (Division of Infectious Diseases) and Microbiology & Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, 10461, New York, USA

    • Arturo Casadevall
    •  & Liise-anne Pirofski

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  2. Search for Liise-anne Pirofski in:

Corresponding author

Correspondence to Arturo Casadevall.

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Glossary

HOST

An entity in which microorganisms reside and/or replicate; an entity in which microbial pathogenesis occurs.

DAMAGE

Disruptions in the normal homeostatic mechanisms of a host that alter the functioning of cells, tissues or organs; for microorganisms, disruptions in the normal mechanisms that enable host entry, replication and/or the ability to establish residence in a host.

MUTUALISM

A state of infection whereby both the host and the microorganism benefit.

COMMENSALISM

A state of host–microorganism interaction that does not result in host damage after the state is initiated.

DISEASE

A clinical outcome of host damage that occurs after a threshold amount of damage has occurred.

MICROBIAL INFECTION

The acquisition of a microorganism by a host.

VIRULENCE

The relative capacity of a microorganism to cause damage in a host.

PATHOGENIC MICROORGANISM

A microorganism that has the capacity to cause damage in a host.

COLONIZATION

A state of host–microorganism interaction that leads to a variable amount of host damage, from minimal to great, thereby reflecting host immune responses that have the capacity to eliminate the microorganism or to promote the development of another state.

LATENCY

A state of host–microorganism interaction in which a microorganism persists in a host and can be associated with damage that can be evident at the cellular or tissue level, but is not associated with disease.

VIRULENCE FACTOR

A microbial component that can damage a host.

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DOI

https://doi.org/10.1038/nrmicro732

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