Review Article | Published:

The co-pathogenesis of influenza viruses with bacteria in the lung

Nature Reviews Microbiology volume 12, pages 252262 (2014) | Download Citation

Abstract

Concern that a highly pathogenic virus might cause the next influenza pandemic has spurred recent research into influenza and its complications. Bacterial superinfection in the lungs of people suffering from influenza is a key element that promotes severe disease and mortality. This co-pathogenesis is characterized by complex interactions between co-infecting pathogens and the host, leading to the disruption of physical barriers, dysregulation of immune responses and delays in a return to homeostasis. The net effect of this cascade can be the outgrowth of the pathogens, immune-mediated pathology and increased morbidity. In this Review, advances in our understanding of the underlying mechanisms are discussed, and the key questions that will drive the field forwards are articulated.

Key points

  • Mortality from influenza viruses is strongly linked to secondary bacterial invaders. In the most extreme example, more than 95% of the 50 million or more deaths during the 1918 pandemic were complicated by bacterial pneumonia.

  • Influenza viruses differ in their propensity to support bacterial superinfection, depending on the expression of particular virulence factors. Nascent pandemic strains that emerge from the avian reservoir naturally possess many such traits; often these are lost over time as the viruses reach an equilibrium with their hosts.

  • Similarly, different strains of bacteria express different virulence factors that enable them to take advantage of virus-mediated alterations to lung physiology and immunity. The regional distribution of these strains probably influences the severity of influenza epidemics and pandemics.

  • Disruption of lung physiology by respiratory viruses breaches natural barriers to infection and promotes bacterial co-infection. Receptors that can be used by bacteria for adherence and infection are uncovered and upregulated.

  • Viruses and bacteria express factors that subvert, inhibit or eliminate host immune responses. Paradoxically, the resulting pathogen overgrowth might lead to augmented inflammatory responses and immune-mediated host damage.

  • Although they are typically secondary invaders during influenza infections, bacteria express virulence factors that promote viral pathogenesis. This results in increased viral load and decreased clearance.

  • There are many key unanswered questions in the field of co-infections. A better understanding of the complex relationships between virus, host and bacteria will aid us in combating common manifestations, such as community-acquired pneumonia, and help us to prepare for the inevitable next severe influenza pandemic.

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  1. Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, Tennessee 38103, USA.

    • Jonathan A. McCullers
  2. Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

    • Jonathan A. McCullers

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The author declares no competing financial interests.

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Correspondence to Jonathan A. McCullers.

Glossary

Influenza pandemic

A worldwide and severe influenza epidemic caused by a virus with a novel haemagglutinin.

Clonotypes

Groups of staphylococcal strains that share similar characteristics, as distinguished by pulsed-field gel electrophoresis.

Dead space

An area of lung that has a mismatch between aeration and perfusion, such that gas exchange cannot take place.

Cytokine storm

A state characterized by cytokine levels that are higher than physiological norms; it is associated with inflammation and organ dysfunction.

α2,3 or α2,6 linkage

Linkages between terminal sialic acids and galactose on host cells; influenza viruses preferentially attach to different sialic acids depending on linkage type.

Intermediate hosts

Hosts such as pigs or domestic poultry, in which a virus first adapts before successfully jumping to humans.

Reassortment

A process by which segmented viruses, such as influenza, can swap genes with one another while co-infecting a cell.

Serotypes

Groups of pneumococcal strains that are distinguished by the antigenicity of their capsules.

Molecular signatures

Specific amino acids that are associated with virulence and co-pathogenesis with bacteria.

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