Tissue macrophages and interferon-gamma signalling control blood-stage Plasmodium chabaudi infections derived from mosquito-transmitted parasites

ABSTRACT Little is known about the function and regulation of splenic γδ T cells during chronic Plasmodium chabaudi malaria. The splenic γδ T-cell population continues to expand, reaching levels equal to 4 times the number of splenocytes in an uninfected mouse. Splenic γδ T cells from JH −/− mice with chronic malaria expressed Vγ1+ or Vδ4+ in the same ratio as uninfected controls with Vγ1 cells dominating, but the Vγ2 ratio declined about twofold. γδ T cells from G8 mice specific for the TL antigen increased only 2-fold in number, compared with 10-fold in BALB/c controls, but G8 γδ T cells failed to express the B220 activation marker. Elimination of the parasite by drug treatment caused a slow depletion in the number of splenic γδ, CD4+, and CD8+ T cells. Following challenge, drug-cured JH −/− mice exhibited nearly identical parasitemia time courses as naïve controls. Depletion of either CD4+ T cells or γδ T cells from chronically infected JH −/− mice by monoclonal antibody treatment resulted in an immediate and significant (P < 0.05) exacerbation of parasitemia coupled with a marked decrease in splenic γδ T-cell numbers. The number of CD4+ T cells, in contrast, did not decrease in mice after anti-T-cell receptor γδ treatment. The results indicate that cell-mediated immunity against blood-stage malarial parasites during chronic malaria (i) requires the continued presence of blood-stage parasites to remain functional, (ii) is dependent upon both γδ T cells and CD4+ T cells, and (iii) lacks immunological memory.

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Cellular Changes and Apoptosis in the Spleens and Peripheral Blood of Mice Infected with Blood-Stage Plasmodium chabaudi chabaudi AS

Infection and Immunity ◽

10.1128/iai.68.3.1485-1490.2000 ◽

2000 ◽

Vol 68 (3) ◽

pp. 1485-1490 ◽

Cited By ~ 85

Author(s):

Helena Helmby ◽

Gun Jönsson ◽

Marita Troye-Blomberg

Keyword(s):

Immune System ◽

B Cells ◽

Peripheral Blood ◽

Fas Ligand ◽

Acute Infection ◽

Cell Types ◽

Absolute Number ◽

Blood Stage ◽

Cellular Interactions ◽

Plasmodium Chabaudi

ABSTRACT Infection with blood-stage Plasmodium chabaudi chabaudiAS results in splenomegaly, peripheral leukocytosis, and a major activation of the immune system. The frequencies and absolute numbers of T-cell, B-cell, and macrophage populations in spleen and peripheral blood from P. chabaudi-infected BALB/c mice were compared and found to be significantly altered during acute infection. The kinetics of the redistribution of the different cell types in spleen and peripheral blood were different, with T and B cells appearing in the blood when their frequencies and absolute numbers in the spleen were low. The frequency and absolute number of apoptotic cells in the spleen were increased during acute P. chabaudi infection and involved both T cells, B cells, and macrophages. Both Fas and Fas-ligand expression were increased in the spleen. Taken together, our data provide new information on the complex cellular interactions that take place in the immune system during blood-stage malaria infection in a mouse model.

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