Role of IL-10 in invasive aspergillosis: increased resistance of IL-10 gene knockout mice to lethal systemic aspergillosis.
IL-10 is associated with a Th2 response, down-regulation of a Th1 response and macrophage activation. We assessed the role of IL-10 during systemic infection with Aspergillus fumigatus. Systemic aspergillosis was established in female C56B1/6 IL-10(-/-) (KO) and wild-type (WT) C57B1/6 mice by i.v. administration of 1 x 10(5)-6 x 10(5) conidia of A. fumigatus. In two experiments, KO survived longer than did WT (P < 0.001). Determination of fungal burdens in the kidneys and brain showed that KO carried significantly lower burdens in both organs than did WT on day 3 (P < 0.001). Semiquantitative histological analyses showed fewer inflammatory foci/mm2 in brain and kidneys of KO than WT (P < 0.03 and < 0.001, respectively) and that extent of infection and associated tissue injury were greater in WT. Although beneficial in some bacterial infections, exogenous IL-10 has been shown deleterious in models of fungal infection. Our data indicate IL-10 is deleterious during systemic aspergillosis infection, increasing the host susceptibility to lethal infection. We speculate this might be related to greater Th2 or lesser Th1 responses, or down-regulation of macrophage responses, in WT compared with KO.
Clemons
K V
KV
Department of Medicine, Santa Clara Valley Medical Center and California Institute for Medical Research, San Jose 95128-2699, USA. Karl.Clemons@slip.net
Grunig
G
G
Sobel
R A
RA
Mirels
L F
LF
Rennick
D M
DM
Stevens
D A
DA
D000818:Animals; D001228:Aspergillosis / Q000209:etiology / Q000276:immunology* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000302:isolation & purification / Q000472:pathogenicity; D001921:Brain / Q000382:microbiology / Q000473:pathology; D015169:Colony Count, Microbial; D005260:Female; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology*; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors
D016753:Interleukin-10