Figure 5
From: Rapamycin adjuvant and exacerbation of severe influenza in an experimental mouse model
Rapamycin salvage impairs virus clearance with suppressed antigen-specific T cell immunity and aggravates overall lung inflammation with severe intra-alveolar edema and hyaline deposition. Naïve BALB/c mice of comparable age received adoptive transfer of 2.5 × 106 naïve HA-specific 6.5 CD4+ T cells with infection of 2.5 × 103 PFU PR8 virus. Rapamycin and Oseltamivir treatment was started from day 2- post infection and control untreated mice received daily intraperitoneal injection of equal volume placebo solvent and oral feeding of phosphate buffered solution (PBS). Mice with Oseltamivir only served as another control group. On day 7- post infection, compared to untreated and Oseltamivir only mice, Rapamycin salvage treatment caused (a) more body weight loss in mice with (b) impaired virus clearance in the lungs. Antigen-specific CD4+ T cell immunity was attenuated with low activation status of the stated immune parameters as well (c). However, the percentage of Foxp-3+ regulatory T cells in the lungs was comparable among all groups of mice. Histological analysis of lung sections revealed severe hyaline deposition and edema with Rapamycin salvage treatment. Besides less lymphocyte infiltration with Rapamycin salvage, infiltration of neutrophil and plasma cells were comparable among all groups of mice (d). All the observed effects of Rapamycin salvage were higher with high dose compared to that with low dose. Data are representative of at least three similar experiments and presented as mean ± s.d. (***p < 0.0001; *p < 0.01; NS = non-significant, p > 0.05; n = 6/group).
