Background:Triggering receptor expressed on myeloid cell-1 (TREM-1) may play a vital role in mammalian target ofrapamycin (mTOR) modulation ofCD8+ T-cell differentiation through the transcription factors T-box expressed in T-cells and eomesodermin during the immune response to invasive pulmonary aspergillosis (IPA).This study aimed to investigate whether the mTOR signaling pathway modulates the proliferation and differentiation ofCD8+ T-cells during the immune response to IPA and the role TREM-1 plays in this process.Methods:Cyclophosphamide (CTX) was injected intraperitoneally,andAspergillusfumigatus spore suspension was inoculated intranasally to establish the immunosuppressed IPA mouse model.After inoculation,rapamycin (2 mg.kg-1·d-1) or interleukin (IL)-12 (5 μg/kg every other day) was given for 7 days.The number of CD8+ effector memory T-cells (T),expression of interferon (IFN)-γ,mTOR,and ribosomal protein S6 kinase (S6K),and the levels of IL-6,IL-10,galactomannan (GM),and soluble TREM-1 (sTREM-1) were measured.Results:Viable A.fumigatus was cultured from the lung tissue of the inoculated mice.Histological examination indicated greater inflammation,hemorrhage,and lung tissue injury in both IPA and CTX + IPA mice groups.The expression of mTOR and S6K was significantly increased in the CTX + IPA + IL-12 group compared with the control,IPA (P =0.01;P =0.001),and CTX + IPA (P =0.034;P =0.032) groups,but significantly decreased in the CTX + IPA + RAPA group (P ＜ 0.001).Compared with the CTX + IPA group,the proportion of Tem,expression of IFN-γ,and the level of sTREM-1 were significantly higher after IL-12 treatment (P =0.024,P =0.032,and P =0.017,respectively),and the opposite results were observed when the mTOR pathway was blocked by rapamycin (P ＜ 0.001).Compared with the CTX + IPA and CTX + IPA + RAPA groups,IL-12 treatment increased IL-6 and downregulated IL-10 as well as GM,which strengthened the immune response to the IPA infection.Conclusions:mTOR modulates CD8+ T-cell differentiation during the immune response to IPA.TREM-1 may play a vital role in signal transduction between mTOR and the downstream immune response.