Co-ordinate but disproportionate activation of apoptotic, regenerative and inflammatory pathways characterizes the liver response to acute amebic infection.
The liver has the remarkable ability to respond to injury with repair and regeneration. The protozoan parasite Entamoeba histolytica is the major cause of liver abscess worldwide. We report a transcriptional analysis of the response of mouse liver to E. histolytica infection, the first study looking at acute liver infection by a non-viral pathogen. Focusing on early time points, we identified 764 genes with altered transcriptional levels in amebic liver abscess. The response to infection is rapid and complex, with concurrent increased expression of genes linked to host defence through IL-1, TLR2, or interferon-induced pathways, liver regeneration via activation of IL-6 pathways, and genes associated with programmed cell death possibly through TNFalpha or Fas pathways. A comparison of amebic liver infection with the liver response to partial hepatectomy or toxins reveals striking similarities between amebic liver abscess and non-infectious injury in key components of the liver regeneration pathways. However, the response in amebic liver abscess is biased towards apoptosis when compared with acute liver injury from hepatectomy, toxins, or other forms of liver infection. E. histolytica infection of the liver simultaneously activates inflammatory, regenerative and apoptotic pathways, but the sum of these early responses is biased towards programmed cell death.
Department of Medicine, Division of Infectious Diseases, Campus Box 8051, Washington University School of Medicine, St. Louis, MO 63110, USA.
Lorraine C
LC
Pelosof
Paul H
PH
Davis
Zhi
Z
Zhang
Xiaochun
X
Zhang
Samuel L
SL
Stanley
D000818:Animals; D017209:Apoptosis; D004748:Entamoeba histolytica / Q000472:pathogenicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007249:Inflammation; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000503:physiopathology*; D008101:Liver Abscess, Amebic / Q000276:immunology / Q000469:parasitology / Q000503:physiopathology*; D008115:Liver Regeneration; D051379:Mice; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D011506:Proteins