T Cells Boost Immunity Against Fungal Pneumonia in Mice

Despite the effectiveness of vaccines for various illnesses, there are still none licensed to prevent or control human fungal infections. This disparity was made even more apparent during the COVID-19 pandemic — countries using steroids to suppress lung inflammation found that COVID-19 patients with preexisting conditions were more likely to develop lethal fungal infections. To address these needs, researchers from the University of Illinois College of Veterinary Medicine used mouse models to find that a specific type of T cell is necessary for the body to acquire immunity against fungal pathogens.

Their study, published in Cell Reports, began by injecting mice with an experimental fungal vaccine before exposure to a virulent fungal pathogen causing lethal pulmonary infection. Then, the team could examine how necessary these specialized T cells, called GM-CSF⁺ Tc17 cells, were to mediate vaccine immunity.

They identified that two cytokines, IL-1 and IL-23, are necessary for eliciting GM-CSF⁺ Tc17 cells to the vaccine. While IL-23 is dispensable for the long-term memory homeostasis of these cells, it’s also essential for immunity against pulmonary fungal infections.

“A particular type of T cell [T_H17 cells] that expresses GM-CSF [granulocyte-macrophage colony-stimulating factor] was linked to greater severity of illness in people infected with the virus that causes COVID-19,” says senior author Dr. Som Nanjappa, assistant professor of immunology at the University of Illinois.

The discovery of a useful T cell subset for fungus vaccine protection in this study supports efforts to create a vaccine platform with acceptable adjuvants to potentiate such a T cell subset. “Our study shows that IL-17A⁺ CD8⁺ T cell (Tc17), which also expresses GM-CSF, is necessary for mediating fungal vaccine immunity without instigating hyperinflammation. So clearly, the antigen specificity of T cells—whether they target viral vs. fungal or bacterial pathogens—has a huge impact on whether they play a protective or detrimental role,” Dr. Nanjappa explains.

“In line with this, we have identified a functional phenotypic marker that could be targeted to enhance this subset to augment vaccine efficacy,” says Dr. Nanjappa, who recently received NIH-R01 funding to pursue this strategy for a fungal vaccine.