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Updated: Mar 17, 2026
Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
mTOR Modulates Lymphocyte Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary
Na Cui1, Long-Xiang Su1, Hao Wang1
1Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
Background:
Aspergillosis infection is common in the patients with insufficient immunity. The role of mammalian target of rapamycin (mTOR), T-box expressed in T-cells (T-bet), and eomesodermin (EOMES) in mediating T lymphocytes differentiation in response to Aspergillus fumigatus infection in immunocompromised rats was investigated in this study.
Methods:
Invasive pulmonary aspergillosis (IPA) of immunosuppressive twenty male rats were established and sacrificed at 24 h (n = 5), 48 h (n = 5), 72 h (n = 5), and 96 h (n = 5) after A. fumigatus infection. In addition, control (n = 5), cyclophosphamide (CTX) (n = 5), and aspergillosis (n = 5) group were also established the tissues and pathology of lung tissue was examined by hematoxylin and eosin staining. CD8+ T-cells was sorted by flow cytometry. Serum mTOR, S6K, T-bet, and EOMES were quantified by enzyme-linked immunosorbent assay.
Results:
Histology of lung tissue indicated severe lung tissue injury including infiltration of inflammatory cells, alveolar wall damage or degradation, blood congestion, and hemorrhage in the CTX, IPA, and CTX + IPA rats. Hyphae were seen in the IPA, and CTX + IPA groups. The proportion of CD8+ T-cells was significantly increased in the animals of CTX + IPA. Memory CD8+ T-cells was significantly increased in early stage (24 h and 48 h, P < 0.001), but decreased in the late phase of fungal infection (72 h and 96 h) in the animals of CTX + IPA. In addition, at early stage of fungal infection (24 h and 48 h), serum mTOR (P < 0.001), S6K (P < 0.001), and T-bet (P < 0.05) was significantly higher, while EOMES was significantly lower (P < 0.001), in CTX + IPA group than that in control, CTX alone or IPA alone group. Conversely, serum mTOR, S6K, T-bet, and EOMES showed opposite changed in the late stage (72 h and 96 h). Pearson's correlation analysis indicated that mTOR and S6K were significantly correlated with T-bet (r = 0.901 and 0.91, respectively, P < 0.001), but negatively and significantly correlated with EOMES (r = -0.758 and -0.751, respectively, P < 0.001).
Conclusions:
mTOR may regulate transcription factors of EOMES and T-bet, and by which mechanism, it may modulate lymphocytes differentiation in animals with immune suppression and fungal infection.
Insights
Mammalian target of rapamycin (mTOR) influences T-cell differentiation during Aspergillus fumigatus infection in immunocompromised rats. This pathway impacts T-box expressed in T-cells (T-bet) and eomesodermin (EOMES) expression, crucial for immune response.
Area of Science:
- Immunology
- Molecular Biology
- Infectious Diseases
Background:
- Aspergillosis is a significant threat to immunocompromised individuals.
- The study investigates the roles of mTOR, T-bet, and EOMES in T lymphocyte differentiation during Aspergillus fumigatus infection.
Purpose of the Study:
- To elucidate the involvement of mTOR, T-bet, and EOMES in T lymphocyte differentiation in an immunocompromised rat model of invasive pulmonary aspergillosis (IPA).
Main Methods:
- Invasive pulmonary aspergillosis was established in immunosuppressed rats.
- Lung tissue and serum samples were collected at various time points post-infection.
- Flow cytometry, hematoxylin and eosin staining, and ELISA were used to analyze CD8+ T-cells, tissue pathology, and protein levels.
Main Results:
- Infection led to severe lung injury and increased CD8+ T-cells, with memory CD8+ T-cells peaking early and declining later.
- Serum levels of mTOR, S6K, and T-bet were elevated in the early stage, while EOMES was decreased, with opposite trends in the late stage.
- mTOR and S6K showed significant positive correlations with T-bet and negative correlations with EOMES.
Conclusions:
- mTOR signaling pathway appears to regulate T-bet and EOMES transcription factors.
- This regulation likely modulates T lymphocyte differentiation in the context of immune suppression and fungal infection.
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