Plasmodium chabaudi adami: use of the B-cell-deficient mouse to define possible mechanisms modulating parasitemia of chronic malaria.
Our previous observation that B-cell-deficient JH-/- mice utilize T cell-dependent immunity to suppress acute Plasmodium chabaudi adami-induced malaria but then develop chronic low-level parasitemia prompted this study of control mechanisms for chronic parasitemia. When we infected JH-/- mice with blood-stage parasites, chronic parasitemia exacerbated after the 6th month and persisted for up to 17 months. This exacerbation of parasitemia could not be attributed to host aging because the time-course of acute infection in naïve aged mice was nearly identical to that seen in young mice. Nor could exacerbated parasitemia be attributed to mutation in the parasite genome resulting in increased virulence; when subinoculated into naïve JH-/- mice, parasites from chronically infected JH-/- mice with exacerbated parasitemia produced acute stage parasitemia profiles in most recipients comparable to those seen in JH-/- mice upon infection with the original stabilate material. Of the pro-inflammatory cytokines measured, including IFNgamma, TNFalpha, IL-12p70, and MCP-1beta, none were significantly different in the sera of mice with exacerbated parasitemia compared to uninfected controls. Levels of IL-6 were significantly (P=0.002) less in the sera of mice with exacerbated parasitemia. Serum levels of the anti-inflammatory cytokine, TGFbeta, were significantly depressed in chronically infected JH-/- mice compared to uninfected controls. In contrast, IL-10 levels were markedly increased. These findings suggest that the cytokine balance may be disturbed during chronic malaria, thereby impacting on mechanisms that modulate levels of parasitemia.
Weidanz
William P
WP
Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706 1532, USA. wweidanz@wisc.edu
Batchelder
Joan M
JM
Flaherty
P
P
LaFleur
G
G
Wong
C
C
van der Heyde
H C
HC
D000375:Aging / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D007111:Immunity, Cellular; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood; D008288:Malaria / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000276:immunology*; D016788:Plasmodium chabaudi / Q000276:immunology* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000097:blood; D014774:Virulence
D016207:Cytokines; D016212:Transforming Growth Factor beta; D016753:Interleukin-10