Insurmountable heat: The evolution and persistence of defensive hyperthermia
Fever, the rise in body temperature set point in response to infection or injury, is a highly conserved trait among vertebrates, and has also been documented in many arthropods. Fever is known to truncate the duration of infection and reduce mortality. These observations present an evolutionary puzzle: why has fever continued to be an effective response to fast-evolving pathogenic microbes over hundreds of millions of years and across diverse phyla? Framing fever as part of a more general thermal manipulation strategy that we term defensive hyperthermia, we hypothesize that the solution to this puzzle lies in the independent contributions to pathogen fitness played by virulence and infectivity. A host organism deploying defensive hyperthermia alters the ecological environment of an invading pathogen. To the extent that the pathogen evolves so as to be able to function effectively at both normal and elevated temperatures, it disadvantages itself in the task of infecting the next host - whose body temperature will be lower - becoming more likely to be thwarted by both that host's immune system and wild ecotype conspecifics that, though more vulnerable to elevated temperatures, operate more effectively at the host's normal temperature. We evaluate this hypothesis in light of existing evidence concerning pathogen thermal specialization, and discuss theoretical and translational implications of this model.