Delayed clearance of intraabdominal abscesses caused by Candida albicans in tumor necrosis factor-α- and lymphotoxin-α-deficient mice

The role of endogenous tumor necrosis factor-alpha (TNF) and lymphotoxin-alpha (LT) in a model of intraabdominal Candida sepsis and abscess formation was investigated. Significantly more abscesses were observed in TNF/LT double knockout (TNF-/-LT-/-) mice, compared with that in wild-type (TNF+/+LT+/+) mice. Outgrowth of Candida in abscesses of TNF-/-LT-/- mice was 10-fold increased on day 14 and 60-fold increased on day 21 of infection. The interleukin-10: interferon-gamma ratio, measured in supernatants of stimulated splenocytes, shifted from 131 for TNF-/-LT-/- mice and 13.9 for TNF+/+LT+/+ mice on day 8 to 0.11 for TNF-/-LT-/- mice and 11.66 for TNF+/+LT+/+ mice on day 14 of infection. The diminished host resistance is explained by an impaired extracellular killing capacity of granulocytes and a delayed development of a T helper 1 response in TNF-/-LT-/- mice. In conclusion, TNF and LT are critical to the stimulation of effector cells that leads to elimination of Candida from abscesses.