Delayed Clearance of Intraabdominal Abscesses Caused byCandida albicansin Tumor Necrosis Factor–α– and Lymphotoxin‐α–Deficient Mice

Abstract

The role of endogenous tumor necrosis factor–α (TNF) and lymphotoxin-α (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-γ 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