[The expression of triggering receptor expresses on myeloid cells receptor-1, T cell-specific transcription factor, and eomesodermin in Aspergillus infected immunosuppressed rats].

OBJECTIVE: To investigate the function of triggering receptor expresses on myeloid cells receptor-1 (TREM-1) in lymphocyte differentiation and regulation of Aspergillus infected immunosuppressed rats.

METHODS: Cyclophosphamide (CTX) was intraperitoneally injected and Fumigatus spore suspension was inhaled by percutaneous tracheostomy to establish the immunosuppressive invasive pulmonary aspergillosis (IPA) rat model. After 24 h, 48 h, 72 h and 96 h inoculation, rats were sacrificed. Lung tissue specimens, bronchoalveolar lavage fluid (BALF), and plasma samples were collected. Plasma and BALF sTREM-1, plasma T cell-specific transcription factor (T-box expressed in T cells, T-bet) and eomesodermin(Eomes) were detected by ELISA. Biopsy specimens of lung tissue were used for periodic acid-schiff (PAS) staining and culture.

RESULTS: The mortality rate of immunosuppressed rats after Aspergillus inhalation for 96 h was as high as 54.4%. Biopsy of lung tissue suggested acute inflammatory cell infiltration, interstitial lung congestion, alveolar structural damage, and visible Aspergillus hyphae in alveoli. Compared with normal control group[(110.50 ± 7.70) ng/L], plasma sTREM-1 in study groups were significantly increased[IPA: (146.77 ± 10.41) ng/L; CXT+ IPA at 24 h: (226.00 ± 11.88) ng/L; CTX+ IPA at 48 h: (200.77 ± 10.63) ng/L; P<0.05], so were T-bet levels[IPA: (561.17 ± 7.23) μg/L; CXT+ IPA at 24 h: (647.00 ± 33.03) μg/L; CTX+ IPA at 48 h: (619.23 ± 87.44) μg/L; control group: (340.03 ± 26.32) μg/L; respectively, P < 0.05]. However, plasma Eomes levels in IPA group, CTX+ IPA at 24 h and 48 h were significantly lower compared with that in normal controls[IPA: (7.96 ± 0.65) ng/L; CXT+ IPA at 24 h: (3.97 ± 0.35) ng/L; CTX+ IPA at 48 h: (4.00 ± 0.74) ng/L; control group: (8.38 ± 0.51) ng/L; respectively, P < 0.001]. Compared with those in CTX+ IPA vaccination after 24 h and 48 h, plasma sTREM-1 [(106.67 ± 7.64) ng/L; (133.27 ± 32.79) ng/L] and T-bet [(299.64 ± 63.07) μg/L; (398.02 ± 109.22) μg/L] in CTX+ IPA at 72 h and 96 h inoculation were significantly lower (P < 0.001). While Eomes [(8.38 ± 0.54) ng/L; (8.40 ± 0.70) ng/L]raised significantly higher (P < 0.001). Compared with the control group, sTREM-1 levels in BALF of IPA+ CTX 24 h, 48 h, 72 h, and 96 h groups were consistently high (P < 0.05). Pearson correlation analysis showed that sTREM-1 and T-bet had a significant positive correlation (r = 0.91, P < 0.001), yet Eomes was negatively correlated with them (r = -0.788, P < 0.001).

CONCLUSIONS: sTREM-1 in rat plasma and BALF appears highly expressed in immune compromised Aspergillus infected rat model. Plasma sTREM-1 is closely correlated with T-bet and Eomes levels, which suggests that TREM-1 may be involved in lymphocytic regulation and differentiation during fungal infection.