Liver cells respond to Aspergillus fumigatus with an increase in C3 secretion and C3 gene expression as well as an expression increase in TLR2 and TLR4.
Fungal infections by molds like Aspergillus fumigatus are an increasing health problem which can be fatal in immuno-compromised patients. In healthy individuals, these infections are easily eliminated by the innate and acquired immune system. Complement factor 3 (C3) has a key place within the complement cascade and C3 RNA expression can therefore be used to monitor an impending immune response. Employing a liver cell line (HepG2) as a model system, we have examined their responses to A. fumigatus or beta-glucan, a major component of the fungal wall. C3 RNA expression was increased after stimulation with both LPS and A. fumigatus as well as after incubation with beta-glucan, although with different kinetics. C3 protein release into the supernatant followed an inverse bell-shaped curve when cells were incubated with A. fumigatus or beta-glucan while during LPS stimulation, the release was more stable. HepG2 cells also express Toll-like receptors (TLRs) and both for TLR2 and TLR4, an expression increase was found. These data demonstrate that liver cells are able to react specifically to a fungal pathogen without the help of Kupffer cells.
Wright
Marianne S
MS
Department of Pediatric Research, Rikshospitalet University Hospital, N-0027 Oslo, Norway. marianne.wright@klinmed.uio.no
Clausen
Hanne K
HK
Abrahamsen
Tore G
TG
D000946:Antigens, Fungal / Q000276:immunology / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000276:immunology / Q000502:physiology*; D002460:Cell Line; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D022781:Hepatocytes / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015854:Up-Regulation; D047071:beta-Glucans / Q000494:pharmacology
D000946:Antigens, Fungal; D003176:Complement C3; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D047071:beta-Glucans; D012313:RNA