mTOR modulates CD8+ T cell differentiation in mice with invasive pulmonary aspergillosis

Abstract

CD8+ T cells are a vital component of the adaptive immune system and important for eliminating intracellular pathogens. Notably, mTOR activity is associated with CD8+ T effector memory (Tem) cell differentiation in fungal infections. This study investigates the molecular mechanisms of CD8+ Tem cell proliferation and differentiation mediated by the mTOR pathway in immunosuppressed mice with invasive pulmonary aspergillosis (IPA). We first established the immunosuppressed IPA mouse model, then mice were subjected to rapamycin treatment daily or interleukin (IL)-12 treatment every other day. Lung tissues and blood samples were obtained seven days later. Aspergillus fumigatus was cultured from the lung tissue of mice inoculated with A. fumigatus spores. After IL-12 treatment, the expression of mTOR and its downstream signaling molecule S6 kinase, number of CD8+ Tem cells and interferon-γ expression were significantly increased, while they were significantly decreased after treatment with rapamycin. Additionally, IL-12 treatment induced T-bet but inhibited Eomesodermin expression, while the opposite was seen when the mTOR pathway was blocked by rapamycin. In conclusion, we found that the mTOR pathway induced CD8+ T cell proliferation and differentiation by regulating T-bet and Eomesodermin expression, which significantly influenced immune regulation during IPA and enhanced the immune response against fungal infection.

Keywords

• cd8-positive t lymphocytes
• invasive pulmonary aspergillosis
• tor serine-threonine kinases
• immunosuppression