Delayed clearance of intraabdominal abscesses caused by Candida albicans in tumor necrosis factor-alpha- and lymphotoxin-alpha-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-10rcolon;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.
Vonk
Alieke G
AG
Nijmegen University Center for Infectious Diseases and Department of Medicine, Nijmegen, The Netherlands.
Netea
Mihai G
MG
van Krieken
Johan H
JH
van der Meer
Jos W M
JW
Kullberg
Bart Jan
BJ
D018784:Abdominal Abscess / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D000818:Animals; D002176:Candida albicans / Q000302:isolation & purification*; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005260:Female; D006098:Granulocytes / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008233:Lymphotoxin-alpha / Q000172:deficiency* / Q000235:genetics; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma