These are bird macrophages infected with the fungal pathogen <i>Cryptococcus neoformans</i> (green). [University of Sheffield]” /><br />
<span class=These are bird macrophages infected with the fungal pathogen Cryptococcus neoformans (green). [University of Sheffield]

For decades, scientists have been searching for the reason why birds can transmit the potentially fatal fungal infection caused by Cryptococcus neoformans, which affects more than one million people annually, yet not become ill themselves. Now, a team of researchers from the University of Sheffield has provided evidence that macrophages within the bird's blood system can completely block the growth of Cryptococcus.

Cryptococcal infections typically cause death among those with weakened immune systems, making them some of the most dangerous infections in individuals with HIV/AIDS. Birds are known to carry the fungus, and their droppings can be a source of human infection; however, the molecular mechanisms preventing the birds from succumbing to the disease has eluded scientists.

One hypothesis was that the avian species' increased internal temperature somehow prevented the fungus from spreading systemically. “Birds have a higher body temperature than humans, 42°C instead of 37°C, but this alone is not enough to fully stop the fungus,” explained lead study author Simon Johnston, Ph.D., research fellow in the department of infection, immunity, and cardiovascular disease at the University of Sheffield. “By studying bird cells under the microscope, we have seen that macrophage cells have the ability to completely block the growth of the fungus, which can be fatal in humans.”

Dr. Johnston and his colleagues found that the fungus can grow slowly within a bird's digestive tract, but if it tries to invade the bird's body, then the immune system immediately destroys it—explaining why healthy birds can still help spread the infection. The findings from this study were published recently in Scientific Reports through an article entitled “Cryptococcus neoformans Thermotolerance to Avian Body Temperature Is Sufficient For Extracellular Growth But Not Intracellular Survival In Macrophages.”

“Understanding where the disease comes from and how it spreads is critical,” Dr. Johnston noted. “If we can learn how some animals are able to resist infection we might be able to gain insights into how we can improve the human immune response to this fungus.”

Looking at pure populations of primary bird macrophages, the researchers were able to detect a small population of C. neoformans that was able to adapt to the inhibitory intracellular environment of bird macrophages. This data allowed the study authors to postulate an infection model “whereby birds can harbor low numbers of Cryptococci for prolonged periods without disease and are therefore able to act as vectors of long-range fungal carriage, and are able to directly inoculate guano.” 

“We are now working with leading scientists from all over the world to try and understand where this pathogen came from, how our bodies fight it, and what we can do to help our own immune system defend us from this fungus and other related infections,” Dr. Johnston added. “Many human diseases are spread by birds, but we know surprisingly little about their immune systems. Discovering how they resist otherwise fatal infections offers the hope of improving our ability to intervene in this cycle and prevent a diverse range of human diseases.”

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