There are two disparate routes through which the immune system can exert its effect. The more readily understood strategy is referred to as resistance in which the immune system is mobilized to detect the offending pathogen and eliminate it. There is, however, another route that the immune system can take and that is tolerance in which the immune system adapts to a certain level of tissue damage inflicted by the offending organism. Interestingly enough, the deleterious impact of infectious disease can be the result of either failed resistance or failed tolerance.
Usually, a deadly outcome of a microbial infection is relegated to either high virulence or decidedly poor resistance on the part of the host immune system. However, there is another possible explanation. The damage produced by an invading pathogen can be directly related to the toxins it produces, or to the inflammatory response precipitated by the immune system that can lead to tissue damage. This latter effect is referred to as “extrinsic virulence.” Insufficient tissue protection and subsequent repair of damaged tissue can also contribute to the lethality of the infectious process.
Dr. Amanda Jamieson and her colleagues at the Howard Hughes Medical Institute and Department of Immunobiology at the Yale University School of Medicine chose to study the co-infection of the influenza virus with Legionella pneumophila using a mouse model as a way of determining whether it is resistance or tolerance on the part of the host immune system that determines lethality.
Through their detailed studies, they found that susceptibility to co-infection occurred even when the bacterial infection was controlled by the immune system. From this, they were able to conclude that the failure of host defenses was directly related to a diminished capacity to tolerate tissue damage.
This is a very interesting finding that may have practical implications regarding the clinical approach to patients whose health is seriously impacted by co-infection.