摘要
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 roTOR signaling pathway modulates the proliferation and differentiation of CD8＋ T-cells during the immune response to I PA and the role TREM-1 plays in this process. Methods： Cyclophosphamide （CTX） was injected intraperitoneally, and Asl？e;gillus.[mnigams spore suspension was inoculated intranasally to establish the immunosuppressed IPA mouse model. After inoculation, rapamycin （2 mg-kg ·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 （Tern）, expression of interferon （IFN）-y, roTOR, and ribosomal protein $6 kinase （S6K）, and the levels of IL-6, IL- 10, galactomannan （GM）, and soluble TREM- 1 （sTREM-I） 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 ＋ I L- 12 group compared with the control, I PA （P = 0.01 ; P - 0.001 ）, and CTX ＋ 1PA （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 Tern, expression of IFN-y, and the level ofsTREM-I 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 roTOR pathway was blocked by rapamycin （P 〈 0.001）. Compared with the CTX ＋ I PA and CTX ＋ I PA ＋ RAPA groups, IL-12 treatment increased IL-6 and downregulated IL- 10 as well as G M, 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.
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 roTOR signaling pathway modulates the proliferation and differentiation of CD8＋ T-cells during the immune response to I PA and the role TREM-1 plays in this process. Methods： Cyclophosphamide （CTX） was injected intraperitoneally, and Asl？e;gillus.[mnigams spore suspension was inoculated intranasally to establish the immunosuppressed IPA mouse model. After inoculation, rapamycin （2 mg-kg ·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 （Tern）, expression of interferon （IFN）-y, roTOR, and ribosomal protein $6 kinase （S6K）, and the levels of IL-6, IL- 10, galactomannan （GM）, and soluble TREM- 1 （sTREM-I） 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 ＋ I L- 12 group compared with the control, I PA （P = 0.01 ; P - 0.001 ）, and CTX ＋ 1PA （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 Tern, expression of IFN-y, and the level ofsTREM-I 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 roTOR pathway was blocked by rapamycin （P 〈 0.001）. Compared with the CTX ＋ I PA and CTX ＋ I PA ＋ RAPA groups, IL-12 treatment increased IL-6 and downregulated IL- 10 as well as G M, 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.
