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Biomedical subjects

D Mazier

Publications and source records attributed to D Mazier.

At least 55 records · Page 3Linked to original sources
PubMed1996

Iron overload increases hepatic development of Plasmodium yoelii in mice.

Iron overload in BALB/c mice by treatment with ferric ammonium citrate promotes the hepatic development of Plasmodium yoelii in vivo and in vitro. This was the result of increased penetration of the parasite into hepatocytes since no effect was observed on parasite transformation or maturation. These results could explain why in endemic regions iron supplementation led, in certain studies, to an increase in clinical episodes of malaria and in the prevalence of malaria infection.

Animals↗
PubMed1996

Experimental model for human intestinal microsporidiosis in interferon gamma receptor knockout mice infected by Encephalitozoon intestinalis.

Interferon gamma receptor knockout mice developed a chronic infection when inoculated with spores of Encephalitozoon intestinalis which is a cause of intestinal microsporidiosis in AIDS patients. The infection was evaluated by enumeration of the spores of the parasite shed in the stools, histological examination and follow up over a period of six months. A dose-response was demonstrated since higher numbers of spores were excreted and more infection sites were found in mice which were given an increased quantity of parasites. In infected wild type mice, the number of excreted spores decreased until day 16 post-inoculation, then spores were detected sporadically in low numbers. These data confirmed the role of IFN-gamma in the control of E. intestinalis infection. The infection was not lethal suggesting that other factors are involved in regulation of the parasite infection. This model, with the long survival time of the animals together with the measurable quantity of spores shed in the stools will be useful for testing potential therapeutical agents.

AIDS-Related Opportunistic Infections↗
PubMed1995

Non specific resistance against malaria pre-erythrocytic stages: involvement of acute phase proteins.

Levels of different acute phase proteins were compared in sera from parasitaemic and non-parasitaemic women living in a Plasmodium falciparum endemic area of Thailand. The ability of their sera to interfere with hepatic stage development of the parasite was examined. Correlations were found between levels of alpha-1 antitrypsin, alpha-2 macroglobulin, hemopexin and the potential of sera to block hepatocyte invasion by the sporozoite.

Acute-Phase Proteins↗
PubMed1995

Immunization with the malaria heat shock like protein hsp70-1 enhances transmission to the mosquito.

Mosquitoes fed on mice infected with Plasmodium yoelii after an immunization with the i72 recombinant form of the heat shock protein hsp70-1 developed significantly more oocysts than mosquitoes fed on controls. This effect was due to a marked increase in the relative numbers of gametocytes during the early stages of infection. A comparison of blood-induced and sporozoite-initiated infection showed that these gametocytes were derived from merozoites released from the liver. The stimulus for increased gametocyte production is unknown but is likely to be linked with antibody-dependent cellular cytotoxicity and associated cytokine responses.

Animals↗
PubMed1995

Protective immunity against malaria: cellular changes in the liver vary according to the method of immunization.

Characterization of cells present in the extravascular compartment of murine liver was performed after different immunization procedures against the malaria parasite Plasmodium yoelii. Mice were immunized with live or irradiated sporozoites or with parasitized erythrocytes. Whatever the immunization protocol used, the mice were protected against a sporozoite challenge but each immunization procedure induced a specific profile of cell types. Immunization with irradiated sporozoite induce a significant increase in CD8+ lymphocytes, parasitized erythrocytes stimulates production of monocytes/macrophages and CD8+ lymphocytes while, after live sporozoites immunization, polymorphonuclear cells, macrophages/monocytes, B cells and a range of T cell subsets were increased in number.

Animals↗
PubMed1995

Effects of iron deficiency on the hepatic development of Plasmodium yoelii.

Iron deficiency through an iron-deficient diet and through an inactivation of hepatic xanthine dehydrogenase (XD) was shown to modulate Plasmodium yoelii sporozoite development in hepatocytes. When mice that are on iron-deficient diet were challenged with sporozoites, enhancement of hepatic stage development was observed, resulting in the earlier appearance of blood parasites. In contrast, inhibition of parasite hepatic development was noticed when iron deficiency was the result of hepatic XD inactivation. In vitro studies have shown that diet induced iron-depletion increases penetration of sporozoites into liver cells while inactivation of hepatic XD resulted in an inhibition of both sporozoite penetration and schizont maturation. Moreover, inhibition of heme synthesis (which requires intrahepatic iron) also led to an inhibition of parasite development.

Animals↗
PubMed1994

Murine AIDS protects mice against experimental cerebral malaria: down-regulation by interleukin 10 of a T-helper type 1 CD4+ cell-mediated pathology.

The retrovirus LP-BM5 murine leukemia virus induces murine AIDS in C57BL/6 mice that has many similarities with human AIDS; Plasmodium berghei ANKA causes experimental cerebral malaria in the same strain of mice. The outcome of malaria infection was studied in mice concurrently infected with the two pathogens. The retrovirus significantly reduced the gravity of the neurological manifestations associated with Plasmodium berghei ANKA infection. The protection against experimental cerebral malaria induced by murine AIDS increased with duration of viral infection and, hence, with the severity of the immunodeficiency. Interleukin 10, principally from splenic T cells, was shown to play a crucial role in this protection.

Animals↗
PubMed1994

Alterations of uninfected red blood cells in malaria.

Red blood cell (RBC) negative charges and resistance to linoleic acid (LNA)-induced lysis were studied in Plasmodium yoelii-infected mice and in malaria (P. falciparum)-affected individuals. RBCs from mice infected with P. yoelii showed a progressive decrease in the net surface negative charges at 24 h after infection, reaching a minimal value on day 3, followed by a second phase that was characterised by a recovery to normal levels on day 6. Resistance to linoleic acid follows similar kinetics. These alterations preceded the appearance of parasites in the peripheral blood. A similar increase in LNA-induced lysis was observed in RBCs from malaria-affected individuals. These early membrane alterations of uninfected RBCs could be responsible for spreading of infection and RBC lysis during infection.

Adult↗
PubMed1994

Characterization of liver lymphomyeloid cells in mice infected with Plasmodium yoelii sporozoites.

We have isolated, characterized and quantified the immunocompetent cells present in the extravascular hepatic compartment at various stages after Plasmodium yoelii malaria infection with sporozoites. Cytological analyses revealed a predominantly lymphoid population. In mice with a primary infection, the predominant cells were CD4+, CD8+ and B lymphocytes. In fully protected mice, CD3+ CD4- CD8- and polymorphonuclear cells, particularly eosinophils, were most common. The significance of changes in subpopulations is discussed in relation to antigen presentation and host-protective mechanisms.

Animals↗
PubMed1993

Effector functions of circumsporozoite peptide-primed CD4+ T cell clones against Plasmodium yoelii liver stages.

Previously, CD4+ T cell lines and clones were isolated after immunization of BALB/c and C57BL/6 mice with the Py1 peptide, a 21-mer synthetic peptide corresponding to a N-terminal segment of the circumsporozoite protein of Plasmodium yoelii. The clones were separated into the Th1 and Th2 subsets on the basis of lymphokine production. It was observed that immunization with the Py1 peptide induced preferentially Th1 cells in BALB/c and Th2 cells in C57BL/6 mice. These clones were then tested for their cytolytic ability in vitro. Some of the clones from BALB/c and C57BL/6 mice eliminated liver stage parasites from cultured hepatocytes in a MHC restricted manner. Nevertheless, none of these clones was able to lyse Py1 peptide-pulsed target cells. It was also found that two clones could protect BALB/c mice against a sporozoite challenge. These results provide evidence that CD4+ T cells, induced after priming with a defined peptide, could participate in the effector mechanisms against malaria liver stages.

Animals↗
PubMed1993

In vivo induction of the nitric oxide pathway in hepatocytes after injection with irradiated malaria sporozoites, malaria blood parasites or adjuvants.

The mechanisms responsible for malarial immunity induced by repetitive injections of X-irradiated sporozoites have not been fully established. We demonstrate here that a single injection of irradiated sporozoites induced, as soon as 24 h after, a non-permissive state to hepatocyte reinfection with sporozoites in vitro. The same effect was observed when malarial blood forms, irradiated promastigotes of Leishmania infantum, adjuvants (muramyl dipeptide, poly acidylic uridylic) or interferon-gamma was injected. Activation of the nitric oxide (NO) pathway in the hepatocyte by these factors was found to be responsible for hepatocyte refractory status. Additionally, this metabolic pathway is involved in protection given by repeated injections of irradiated sporozoites since protection could be reversed by treating mice at the time of sporozoite challenge with a competitive inhibitor (NG-monomethyl-L-arginine) of the NO pathway. These results suggest that, in view of an antisporozoite vaccine, further studies are needed to find out how to activate specifically a long-lasting nonspecific immune response.

Adjuvants, Immunologic↗
PubMed1993

The role of reactive nitrogen intermediates in modulation of gametocyte infectivity of rodent malaria parasites.

Direct feeding of Anopheles stephensi mosquitoes on mice infected with Plasmodium vinckei petteri showed that, during the periods of schizogony in the blood, the infectivity of gametocytes was markedly reduced. This could be prevented by prior injection of the L-arginine analogue, Nw-nitro-L-arginine (NwNLA) showing that the altered infectivity was due to reactive nitrogen intermediates (RNI). Similar effects on transmission of P. yoelii nigeriensis were demonstrated in vitro by membrane feeding of the mosquitoes. The in vitro reduction in infectivity could be reversed by injecting the L-arginine analogue either into the infected mouse donor of serum, or into the membrane feeding chamber. Elevated levels of TNF and IL-6 were demonstrated during the course of infection but did not correlate well with nitrogen radical activity. Similarly, direct measurements of NO2- and NO3- did not reflect the nitrogen radical activity revealed by addition of the specific L-arginine analogue.

Animals↗
PubMed1993

Hepatic stages of malaria: specific and non-specific factors inhibiting the development.

Protection against pre-erythrocytic stages of malaria is possible, as demonstrated by the resistance obtained by immunizing with irradiated sporozoites. However, the involved mechanisms are more numerous and intricate than previously believed. Recently, the hepatic stage, rather than the sporozoite stage, has been seen as the target of immune attack.

Animals↗
PubMed1992

IL-6 induced by IL-1 inhibits malaria pre-erythrocytic stages but its secretion is down-regulated by the parasite.

The capacity of IL-6 to mediate the antiparasitic activity of IL-1 on intrahepatic development of malaria parasite was demonstrated. The comparisons of IL-6 levels in infected and noninfected hepatocyte cultures, either purified or enriched with nonparenchymal cells and stimulated by IL-1 or IL-6, indicate that subtle interactions exist between intrahepatocytic development of Plasmodium yoelii and liver synthesis of IL-6. During its intrahepatic multiplication, the parasite causes a decline in IL-6 production. IL-6 mRNA was not detected in the livers of infected mice during development of either hepatic or blood stage parasites although IL-6 activity was found in the sera during both stages.

Animals↗
PubMed1992

The role of interleukin-6 in vitamin A deficiency during Plasmodium falciparum malaria and possible consequences for vitamin A supplementation.

Kinetics of serum levels of interleukin-6 (IL-6) were studied in patients with acute Plasmodium falciparum malaria in relation to vitamin A and its binding proteins, retinol binding protein (RBP) and pre-albumin. It was found that IL-6 levels followed the rise and decrease of parasitaemia by 12 hr and correlated inversely with levels of vitamin A and its binding proteins. These data suggest that vitamin A supplementation alone might still be insufficient to restore a malaria-induced vitamin A deficiency.

Adult↗
PubMed1991

In vitro activity of CD4+ and CD8+ T lymphocytes from mice immunized with a synthetic malaria peptide.

In previous work, a T-helper epitope was mapped within the circumsporozoite protein of the murine malaria parasite Plasmodium yoelii. A 21-mer synthetic peptide corresponding to this epitope (amino acid positions 59-79; referred to as Py1) induced a specific T-cell proliferation in BALB/c and C57BL/6 mice and provided help for the production of antibodies to peptides from the repetitive region, (Gln-Gly-Pro-Gly-Ala-Pro)n, of the P. yoelii circumsporozoite protein when mice were immunized with the Py1 peptide conjugated to the repetitive peptide. Experiments were then designed to study the in vitro antiparasite efficacy of T cells elicited in vivo by peptide immunization. T-cell activity was evaluated on cultured hepatic stages of P. yoelii. Peptide immunizations led to the preferential activation of CD8+ T cells in BALB/c mice and of both CD4+ and CD8+ T cells in C57BL/6 mice. Parasite elimination was mediated directly by these cells and did not seem to be dependent on lymphokine secretion. These data suggest that peptide-primed CD4+ T cells as well as CD8+ T cells could be cytolytic for the hepatic phase of malaria parasites. The fact that the same peptide could activate different lymphocyte populations, depending on the strain of mouse, highlights the importance of a better understanding of the fine mechanisms behind the immune responses to synthetic peptides being tested for malaria vaccine development.

Animals↗
PubMed1991

L-arginine-dependent destruction of intrahepatic malaria parasites in response to tumor necrosis factor and/or interleukin 6 stimulation.

There is growing evidence that cytokines (interleukin [IL] 1, IL 6, interferon-gamma, tumor necrosis factor [TNF]) directly or indirectly interfere with the intrahepatic development of malaria parasites. Recent work in our laboratory clearly showed that TNF can affect the hepatic development of parasites via IL 6 secreted by liver nonparenchymal cells. The possible participation of an L-arginine-dependent effector mechanism has been studied to explain the TNF/IL 6-induced inhibition. We thus investigated if NGmonomethyl-L-arginine and N omega-nitro-L-arginine, two specific inhibitors of inorganic nitrogen oxide synthesis from L-arginine, were able to affect the inhibitory effect of TNF and/or IL 6 in co-cultures. At 0.1 and 0.5 mM both L-arginine analogues reversed the inhibitory effect of these cytokines. An interesting observation is that L-arginine analogues enhance schizont development in the absence of prior cytokine contact. This result indicates an hepatic basal L-arginine-dependent anti-parasitic activity which might explain the existence of self-degenerating hepatic forms as previously reported.

Animals↗