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.