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It's a common enough occurrence: You're sick as a dog with a cold, but the person in the office next door just has a few sniffles. What accounts for this difference? Most commonly, these sorts of differences are chalked up to differences in resistance—perhaps you have higher viral loads than your office mate. But such differences can also involve differences in the ability to tolerate the same amount of virus. Deciphering the contribution of resistance versus tolerance, however, is difficult. Jamieson et al. (p. 1230, published online 25 April) studied a mouse model of viral and bacterial co-infection where tolerance and resistance could be separated. Mice infected with influenza virus were more likely to succumb to a secondary infection with Legionella pneumophila as a result of impaired tolerance to tissue damage, rather than because of a difference in bacterial burden.
Secondary bacterial pneumonia leads to increased morbidity and mortality from influenza virus infections. What causes this increased susceptibility, however, is not well defined. Host defense from infection relies not only on immune resistance mechanisms but also on the ability to tolerate a given level of pathogen burden. Failure of either resistance or tolerance can contribute to disease severity, making it hard to distinguish their relative contribution. We employ a coinfection mouse model of influenza virus and Legionella pneumophila in which we can separate resistance and tolerance. We demonstrate that influenza virus can promote susceptibility to lethal bacterial coinfection, even when bacterial infection is controlled by the immune system. We propose that this failure of host defense is due to impaired ability to tolerate tissue damage.