Beyond Fever: Fungal infections and the benefits of body heat

Histopathologic features of aspergillosis incl...
Histopathologic features of aspergillosis including the presence of conidial heads PHIL 4335 lores (Photo credit: Wikipedia)

So far on this site I’ve tried to address microbiology topics from all areas of the field; from the standards in bacteriology and virology to some more exotic parasites and fungal infections. When you look at the range of infections that people can acquire you see many bacteria, viruses, and parasites. However, invasive fungal infections, especially those that occur in healthy immune-competent hosts, are exceedingly rare when you compare mammals to insects, plans, and amphibians. I never gave this much thought until coming across a group of papers that together indicate that something as fundamental as a warm body temperature could protect us from a variety of pathogenic fungi.

Read on to see how endothermy may be a protective mechanism against fungal disease.

The world that we live in is filled with fungi and their spores. We come into contact with them on a continual basis, but only a relatively rare minority of us will develop invasive fungal disease. In fact, many of these diseases are so rare that we don’t actually have a concept of what dangers fungi pose. Many of us now are aware of dangers of fungal meningitis due to the distribution of contaminated steroid lots in the US this last summer with disastrous results. Additionally, as the immune-compromised segments of society have grown due either to disease (HIV) or immune-suppression (many medical treatments) we have seen a corresponding proliferation in the number of invasive and deadly fungal diseases that humans can suffer.

Thankfully, most of us who are immune competent will never have to worry about these diseases due to the simple fact that we are warmer than our environments and therefore warmer than many fungi can handle. Mammalian body temperatures in the 30° -40° C are held continually at that temperature and form a distinct thermal microenvironment compared to the world at large.  While this isn’t a specific mechanism in the way that an adaptive immune response is, endothermy appears to be an effective means of restricting fungal infections in mammals. A 2009 paper sampling 4802 different strains of fungi showed that for every 1° C increase in the mammalian temperature range roughly 6% of fungal isolates lost the ability to grow successfully1.  With the human body temperature at 37° we are in a rather privileged zone of thermal exclusion and safe from many fungi by virtue of body temperature.

Frequency histogram of thermal growth tolerance for 4802 fungal strains (bars). Lines connect percentages for 49 mammalian (blue) and 12 bird (red) species core temperatures. Obtained from Mc. Nab [4].
Frequency histogram of thermal growth tolerance for 4802 fungal strains (bars). Lines connect percentages for 49 mammalian (blue) and 12 bird (red) species core temperatures. Obtained from Mc. Nab [4].
Why not stop with a body temperature of 37° C? If mammals developed endothermy and this trait was selected for by evolution (lower fungal disease burden = more fit breeding individuals) then why aren’t body temperatures even higher? According to Figure 1 from the Robert paper very few fungi could hope to grow at 45° C, so why aren’t we 45° C?

There is a trade-off for this protection.  As with everything in life, endothermy has its metabolic costs because as the body becomes warmer it takes more energy to keep a thermal gradient against the environment. A second paper in 2010 attempted to model this tradeoff using a rather ingenious equation to model the fitness of an organism (in terms of metabolic cost and relative fungal exclusion) as a function of body temperature. What resulted is a distinct pattern where the maximum metabolic bang for your buck (as far as avoiding fungi is concerned) is approximately 37° C2.

Organism fitness as a function of body temperature. We normalized fitness, (W(T), to attain a maximum value of 1 and plotted body temperature in decrees Celsius over a range of 27 C to 60 C. Fitness reaches a maximum value at Wmax(T)~ 36.7 C.
Organism fitness as a function of body temperature. We normalized fitness, W(T), to attain a maximum value of 1 and plotted body temperature in decrees Celsius over a range of 27 C to 60 C. Fitness reaches a maximum value at Wmax(T)~ 36.7 C.

So this is why mammalian body temperatures only get so high; it begins to cost too much energy for the relative benefit of excluding only a few more fungi.

We also have another thermal last-line of defense against fungal pathogens: fever.

While not a long-term solution by any means, it is possible the 1°-4°C increase in temperature that occurs during fever could work to limit a remainder of fungal pathogens capable of replicating at 37°C. This enhanced thermal gradient could provide protection by either directly killing off the fungus or by stalling growth long enough for the immune system to clear the infection. Fever is a well-known response to many viral, bacterial, and parasitic infections and it serves that this mechanism would be effective against some fungal pathogens as well.

These papers taken together hint how the maintenance of a thermal gradient against the environment serves to protect mammals from a variety of fungal pathogens by benefit of thermal exclusion well beyond just the few degrees of temperature increase that we see during fevers. These are interesting studies that potentially point to a very simple mechanism by which endotherms have protected themselves from the world of fungi that we live in.

Works Cited:

1.           Robert, V. A. & Casadevall, A. Vertebrate endothermy restricts most fungi as potential pathogens. The Journal of infectious diseases 200, 1623–6 (2009).

2.           Bergman, A. & Casadevall, A. Mammalian endothermy optimally restricts fungi and metabolic costs. mBio 1, (2010).

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