The mouse model of amebic colitis reveals mouse strain susceptibility to infection and exacerbation of disease by CD4+ T cells.
Amebic colitis is an important worldwide parasitic disease for which there is not a well-established animal model. In this work we show that intracecal inoculation of Entamoeba histolytica trophozoites led to established infection in 60% of C3H mice, while C57BL/6 or BALB/c mice were resistant, including mice genetically deficient for IL-12, IFN-gamma, or inducible NO synthase. Infection was a chronic and nonhealing cecitis that pathologically mirrored human disease. Characterization of the inflammation by gene chip analysis revealed abundant mast cell activity. Parasite-specific Ab and cellular proliferative responses were robust and marked by IL-4 and IL-13 production. Depletion of CD4(+) cells significantly diminished both parasite burden and inflammation and correlated with decreased IL-4 and IL-13 production and loss of mast cell infiltration. This model reveals important immune factors that influence susceptibility to infection and demonstrates for the first time the pathologic contribution of the host immune response in amebiasis.
Houpt
Eric R
ER
Division of Infectious Diseases, Department of Medicine, University of Virginia School of Medicine, 300 Lane Road, Charlottesville, VA 22908, USA.
Glembocki
David J
DJ
Obrig
Tom G
TG
Moskaluk
Christopher A
CA
Lockhart
Lauren A
LA
Wright
Rhonda L
RL
Seaner
Regina M
RM
Keepers
Tiffany R
TR
Wilkins
Tracy D
TD
Petri
William A
WA
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D002432:Cecum / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D002455:Cell Division / Q000276:immunology; D002908:Chronic Disease; D006224:Cricetinae; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D004404:Dysentery, Amebic / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology / Q000517:prevention & control; D004748:Entamoeba histolytica / Q000254:growth & development / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000469:parasitology; D007413:Intestinal Mucosa / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012720:Severity of Illness Index; D013045:Species Specificity
D000913:Antibodies, Protozoan