Researchers at the University of Illinois College of Veterinary Medicine have demonstrated in a mouse model that a specific type of T cell, one of the body’s powerful immune defenses, produces cytokines that are needed to that the body acquires immunity against fungal pathogens. This discovery could be instrumental in the development of new effective fungal vaccines.
Although vaccines are hailed as one of medicine’s greatest achievements, responsible for controlling or eradicating many life-threatening infectious diseases, no vaccines have been licensed to prevent or control human fungal infections.
This lack has proven particularly deadly during the COVID-19 pandemic. In countries where steroids were widely used to suppress lung inflammation, COVID-19 patients with pre-existing conditions such as uncontrolled diabetes showed a higher likelihood of developing life-threatening fungal infections.
T cells could produce a protective or pathological response
A special type of T cell [TH17 cells] which expresses GM-CSF [granulocyte-macrophage colony-stimulating factor] was linked to greater disease severity in people infected with the virus that causes COVID-19. »
Dr. Som Nanjappa, Assistant Professor of Immunology, University of Illinois
“Our study shows that IL-17A+ CD8+ The T cell (Tc17), which also expresses GM-CSF, is required to mediate fungal vaccine immunity without causing hyperinflammation. It is therefore clear that the antigenic specificity of T cells – whether they target viral or fungal or bacterial pathogens – has a huge impact on their protective or detrimental role.
The article, “GM-CSF+ Tc17 cells are required to boost vaccine immunity against fatal fungal pneumonia without causing overt pathology”, appeared in Cell reports October 25. Co-authors of Dr. Nanjappa’s study are Srinivasu Mudalagiriyappa, a former graduate student now a scientist at Insmed Incorporated, a global biopharmaceutical company focused on serious and rare diseases; Jaishree Sharma, graduate student in the Department of Pathobiology; and Miranda D. Vieson, clinical associate professor in the Department of Pathobiology and resident veterinary pathologist in the college’s veterinary diagnostic laboratory.
T cells for immunity to fungal vaccines
In the study, colonies of mice received an experimental fungal vaccine. The mice were then exposed to a virulent fungal pathogen to cause a fatal lung infection. Researchers could determine the need for GM-CSF+ Tc17 cells to mediate vaccine immunity. Additionally, they discovered that the cytokines IL-1 and IL-23 are required to trigger GM-CSF+ Vaccine Tc17 cells. While IL-23 is essential for the long-term memory homeostasis of these cells, it is essential for vaccine immunity against lung fungal infections.
This study identifies a beneficial T cell subset for fungal vaccine immunity that bolsters efforts to develop a vaccine platform containing appropriate adjuvants to potentiate such a T cell subset.
“Consistent with this, we have identified a functional phenotypic marker that could be targeted to enhance this subset to increase vaccine efficacy,” Dr. Nanjappa said. He recently received NIH-R01 funding to pursue this strategy for a fungal vaccine.
Mudalagiriyappa, S., et al. (2022) GM-CSF+ Tc17 cells are required to enhance vaccine immunity against fatal fungal pneumonia without causing overt pathology. Cell reports. doi.org/10.1016/j.celrep.2022.111543.