BCG-malaria co-Infection has paradoxical effects on C57BL/6 and A/J mouse strains.
Bacillus Calmette-Guérin (BCG) infection of the spleen is a potent modifier of splenic function. Prior to malaria infection, we infected two mouse strains of differing susceptibility to Plasmodium chabaudi AS (C57BL/6 and A/J) with this mycobacterium. We then evaluated aspects of spleen cell composition, architecture and cytokine expression, and correlated these with the outcome. BCG preinfection resulted in protection of the A/J mice but paradoxically resulted in mortality of the C57BL/6 mice. The latter developed higher parasitaemias that peaked earlier than the A/J mice rendered resistant by BCG. BCG infection induced remarkable changes to splenic histology examined by H&E staining, but there were no consistent differences between mouse strains. C57BL/6 mice had higher absolute numbers of all immune cell phenotypes than did A/J mice, and higher macrophage and dendritic cell proportions. BCG-induced resistance in A/J mice was associated with an increased CD4+ expression of IFN-gamma whilst induced death in C57BL/6 mice was associated with excessive IFN-gamma expression. A moderate TH1 response in the A/J model may have been responsible for the improved survival, and an excessive TH1 response in the C57BL/6 model may have contributed to their death.
Leisewitz
A L
AL
Department of Veterinary Tropical Diseases, Onderstepoort, South Africa. andrew.leisewitz@up.ac.za
Rockett
K
K
Kwiatkowski
D
D
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology*; D018512:Parasitemia / Q000276:immunology; D016788:Plasmodium chabaudi / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D013163:Splenomegaly; D016176:T-Lymphocyte Subsets / Q000276:immunology
D001500:BCG Vaccine; D007371:Interferon-gamma