Mechanisms of virus-induced bacterial superinfections of the lung

This review is intended to show the mechanisms by which respiratory viruses alter pulmonary antibacterial defenses, addressing specifically the problem of bacterial superinfections associated with influenza virus. From the accrued data it appears that the spectrum of the virus-induced damage runs along the defenses of the entire respiratory tract, from bacterial colonization in the nasopharynx to a functional paralysis of the phagocytic cells in the distal lung. Clearly, multiple mechanisms are involved in the virus-induced suppression of pulmonary antibacterial defenses and to invoke a single mechanism as the cause of viral-associated bacterial superinfections would be an over-simplification. The observation that not all viral pneumonias predispose to bacterial superinfections suggests that conditions must be appropriate for the phenomenon to occur. Undoubtedly the magnitude of the virus-induced alterations is an important factor. Qualitatively this means that all the defenses may have to be affected by the virus-infection for the bacterial disease to ensue. For example lung macrophage dysfunction alone may not be sufficient for the inception of secondary bacterial pneumonia if the upper respiratory tract were not colonized with potentially pathogenic bacteria and a mechanism did not exist for a sufficient number of these organisms to reach the deep lung to initiate infection. Quantitatively, it may mean that threshold limits for virus-induced impairment of lung defenses exist and must be surpassed for the inception of bacterial superinfections. Support for this hypothesis comes from the observation that infection with low doses of virus only suppresses the antibacterial defenses of the lung as quantitated by a slower rate of intrapulmonary bacterial inactivation when compared to that in noninfected controls. On the other hand, infection with large doses of virus leads to a failure of pulmonary antibacterial defenses resulting in the rapid proliferation of the bacteria and the demise of the host from overwhelming bacterial infection. Other factors, of course, must also be considered in the etiology of viral-associated bacterial superinfections. Inhalation of pollutants, smoking, alcoholic intoxication, and a number of other exogenous agents are known to alter the defense mechanisms of the lung. These exogenous agents appear to act as concomitant stressors with viral infection which further aggravates the antibacterial defenses of the lung. Finally, endogenous host factors determined by the genetic endowment of the individual, life experiences, nutritional status, and pre-existing disease conditions undoubtedly also modulate viral-associated bacterial superinfections. Lastly, as influenza virus infections occur most frequently in epidemic outbreaks, the relationship between influenza virus and secondary bacterial infections is the classic example. However, there is growing evidence that an association exists between other virus groups and bacterial pathogens in respiratory tract infections. Adenovirus, parainfluenza virus, and rhinovirus are among the agents that appear to pave the way for bacterial pneumonia. Mycoplasma pneumoniae, once considered to be a virus and the cause of primary atypical pneumonia, may also render the respiratory tract susceptible to bacterial invasion.