Differential regulation of murine Mesocestoides corti infection by bacterial lipopolysaccharide and interferon-gamma.
Many liver-invasive parasites cause extensive liver damage which may result in an impaired ability to catabolize endotoxin. The influence of endogenous endotoxin on the progress of liver-invasive parasitic diseases has been investigated in murine Mesocestoides corti infection. Invasion of liver tissue by tetrathyridia resulted in extensive parenchymal destruction with fibrosis. In association with this, undetoxified endotoxin, in potentially biologically active concentration, was found on peritoneal macrophages, 5 months post-M, corti infection. Host susceptibility was influenced by the Lps gene for responsiveness to lipopolysaccharide (LPS). The parasite burden of LPS-responsive (C3H/HeN) mice was significantly increased in the livers of these mice when compared to LPS-resistant (C3H/HeJ) mice. LPS reduced the ability of normal peritoneal macrophages to kill tetrathyridia, when co-cultured in vitro. LPS also abrogated the ability of recombinant interferon-gamma (r.IFN-gamma) to enhance macrophage larvicidal activity. These in vitro findings were confirmed in vivo. Daily intraperitoneal administration of LPS, at low concentration, caused a 4-fold increase in parasite burden in the liver, while r.IFN-gamma at optimal concentration reduced parasite burden by 57%. Post-infection macrophages have previously been shown to be refractory to cytokine-activation for larval killing. In this report, we conclude that (1) this refractoriness may be due to the presence of undetoxified endotoxin on post-infection macrophages and (2) endotoxin may reduce host resistance by abrogating effector macrophage response to IFN-gamma.
Jenkins
P
P
Department of Veterinary Pathology, University of Liverpool.
Dixon
J B
JB
Haywood
S
S
Rakha
N K
NK
Carter
S D
SD
D000818:Animals; D002590:Cestode Infections / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D004198:Disease Susceptibility; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D008099:Liver / Q000469:parasitology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008645:Mesocestoides / Q000254:growth & development / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010529:Peritoneal Cavity / Q000166:cytology; D011994:Recombinant Proteins; D013997:Time Factors
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D007371:Interferon-gamma