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Figure: The GM-CSF+ and IL-17A+ lineages of T cells play an important role in the control of many fungal and bacterial infections and are associated with
autoimmune pathology.
This study shows that GM-CSF expression of Tc17 cells is necessary to
mediate fungal vaccine immunity without enhancing pathology.
Researchers at the University of Illinois College of Veterinary Medicine demonstrated in mouse models that a specific type of T cell (one of the body's powerful immune defense systems) produces cytokines that are necessary for the body to
gain immunity against fungal pathogens.
The discovery could help develop new, effective fungal vaccines
.
Although vaccines have been hailed as one of the greatest achievements in medicine, capable of controlling or eradicating many life-threatening infectious diseases, no vaccine has been approved for the prevention or control of fungal infections
in humans.
This lack has proven especially fatal
during the COVID-19 pandemic.
In countries where steroids are widely used to suppress lung inflammation, people with COVID-19 who have had a previous medical condition such as diabetes are more likely to develop a fatal fungal infection
.
A special type of T cell [TH expressing GM-CSF (granulocyte-macrophage colony-stimulating factor) in 17 cells, has been associated with more severe disease in people infected with
the COVID-19 virus.
"Our study shows that IL-17A+ CD8+ T cells (Tc17), which also express GM-CSF, are necessary
to mediate immunity to fungal vaccines without triggering hyperinflammation.
So it's clear that the antigen specificity of T cells — whether they target viral, fungal, or bacterial pathogens — has a huge impact
on whether they play a protective or harmful role.
”
In the study, a group of mice were injected with an experimental fungal vaccine
.
The mice were then exposed to deadly fungal pathogens to cause fatal lung infections
.
Researchers can determine the necessity of GM-CSF + Tc17 cells mediate vaccine immunity
.
In addition, they found that IL-1 and IL-23 cytokines are necessary to induce GM-CSF + Tc17 cells versus vaccinesAlthough IL-23 is dispensable for long-term memory homeostasis of these cells, it is essential
for vaccine immunity to pulmonary fungal infections.
This study identified a subset of T cells that is immune to fungal vaccines, which has facilitated efforts to develop vaccine platforms containing appropriate adjuvants to enhance such a subset
of T cells.
Dr Nanjappa said: "Based on this, we have identified a functional phenotypic marker that can target this subset of enhancement to enhance the efficacy
of the vaccine.
" He recently received an NIH-R01 grant to implement this strategy
for fungal vaccines.
