Figure 6.

Delayed intrathecal XPro1595 treatment after T3Tx improves antibacterial immunity in chronic SCI animals. At 8 weeks post-SCI, T3Tx-Saline and T3Tx-XPro1595 animals were intracheally administered S. pneumoniae and sickness behavior was tracked for 10 d. Uninjured animals were similarly infected for comparison. a, After infection, 37.5% (3/8) of T3Tx-Saline animals died. No uninjured (0/6) or T3Tx-XPro1595 (0/7) animals died after infection – these latter groups had a 100% survival rate. b–d, Uninjured, infected animals exhibited decreased body weight, increased body temperature, and increased respiratory rate, indicative of sickness. T3Tx-Saline animals exhibited an even greater degree of weight loss, fever, and tachypnea than uninjured and T3Tx-XPro1595 animals. T3Tx-Saline animals were unable to recover to normal bodyweight (b) but recovered back to normal body temperature (c) and respiratory rate (d). T3Tx-XPro1595 animals also exhibited sickness behavior but they recovered to normal bodyweight (b) and did not have as high a peak body temperature (c) or respiratory rate (d). e–i, Lungs were harvested 10 d after infection and homogenates were plated onto blood agar plates. Lungs from naive (i.e., uninfected, uninjured) animals were also harvested and cultured as an additional control. Colony forming units (CFU) were counted 48 h later. There were some CFU in lung cultures from infected, uninjured animals, suggesting that S. pneumoniae was not completely cleared from the lungs (f,i). Cultures from T3Tx-Saline animals' lungs (g) had more CFUs than those from uninjured-infected animals (f), indicating that T3Tx reduces bacterial clearance, indicative of diminished immune function. Cultures from XPro1595-treated animals (h) had fewer CFUs than saline-treated animals and were similar to uninjured-infected animals (i). n = 5–7/group. Mean ± SEM **p < 0.01; ***p < 0.001.