The Spleen in Murine Plasmodium Chabaudi Adami Malaria: Stromal Cells, T Lymphocytes, and Hematopoiesis

Abstract

Morphologic and functional changes in the spleen of BALB/cByJ mice in the course of Plasmodium chabaudi adami malaria were assessed by light and electron microscopy, augmented by probes of polystyrene spheres and autoradiography of injected 3H-uridine-labeled T lymphocytes. The initial phase of the disease (precrisis) was characterized by increasing parasitemia accompanied by a marked increase in spleen size and by anemia. Erythropoiesis predominated, but there was also plasmacytopoiesis and monocyte-macrophage differentiation. The white pulp increased due to enlargement of lymphatic nodules, and in the periarterial lymphatic sheath, plasma cells invade the area around the central artery. A decrease in splenic uptake was demonstrated by light microscopic analysis of concentration and distribution of intravenously injected, spleen-cleared polystyrene spheres. Stromal cells showing signs of intense protein secretion and increased branching were present. Branches of these cells, barrier cells, appeared to seal off from the blood the locules of filtration beds, protecting splenic erythropoiesis from parasitization. Barrier cells are recently recognized fibroblastic contractile stromal cells that fuse to form complex branched variform barriers used for such diverse functions as controlling blood flow and blood cell delivery into the circulation, sealing off the hematopoietic/immunologic colonies and regulating their proliferation and differentration through paracrine secretion. Normally present in marrow and spleen in limited numbers, barrier cells are quickly mobilized in hematopoietic/ immunologic stess. They may well be part of a larger system that includes the myofibroblasts of wound healing and myoepithelial cells. The following phase, crisis, was characterized by a sharp decrease in parasitemia, increased splenic uptake, and amelioration of the anemia. Again, the filtration beds were opened to the blood. In the succeeding phase of postcrisis, the structure of the spleen approached normalcy. Analysis of autoradiographs showed T cells from normal or immunized mice distributing equally to red pulp and white pulp at 1 hr after injection of isolated radioactively labeled T cells, but they increased in white pulp over time. A higher percentage of immune cells was found in the white pulp of mice on day 16 of infection, suggesting a role for these cells in the development of crisis. Interleukin-I-treated mice developed higher levels of parasitemia and lower levels of splenic uptake.

Massive Destruction of Malaria-Parasitized Red Blood Cells despite Spleen Closure

“…1B and C). This state of the spleen, referred to as "closed" below, has been reported to occur transiently in nonlethal infections with P. yoelii 17XNL (32) and P. chabaudi adami (2). However, the data in Fig.…”

“…When the precrisis phase culminates in peak parasitemia, reopening of the filtration beds is associated with an increased trapping activity that is presumably due to malaria-induced splenomegaly (32), and this has been correlated with rapidly decreasing parasitemia in the following crisis phase. In another avirulent malaria model, Plasmodium chabaudi adami infection of BALB/c mice, such transient changes in trapping were further substantiated using fluorescent polystyrol particles (2). By contrast, Yadava et al (36) did not find, with exactly the same parasite/host combination, any evidence for reduced splenic trapping of either Salmonella enterica serovar Typhimurium in the MZ or pRBC in the red pulp, and they concluded that the pRBC avoid a fully functional MZ.…”

Cross-species malaria immunity induced by chemically attenuated parasites

“…For example, we know that immunized mice depleted of CD4 + T cells offer more resistance to infection than naive mice, suggesting that immune cells other than CD4 + T cells might also contribute to protection. Changes in splenic architecture have also been reported in mice following P. yoelii and P. chabaudi infection (28,29), and we cannot rule out the possibility that vaccine-induced immunity occurs with structural changes in the spleen or other tissues. Furthermore, it is known that the liver can play an important role in protection (25,26).…”

Elevated Levels of thePlasmodium yoeliiHomologue of Macrophage Migration Inhibitory Factor Attenuate Blood-Stage Malaria

“…Relative to control parasites, mice were able to resist infection with Py17XL-MIF(ϩ) to a significant degree, as evidenced by a prolonged period of infection and a reduction in the overall mortality rate. During malaria, the spleen is essential for the control of infection and the development of protective immune responses (1,32,59). Our preliminary studies of splenic mRNA levels of TNF-␣, IL-6, IL-12, murine MIF, IL-10, and TGF-␤ showed no differences between Py17XL-MIF(ϩ)-infected and Py17XL-GFPinfected mice.…”