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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malaria infection dramatically induces two nonspecific perturbations in immune responsiveness, polyclonal B cell activation and immunosuppression. Polyclonal activation occurs early in infection and results in secretion of antibodies that lack antiplasmodial specificity. Immunosuppression occurs later in infection and is characterized by blunted humoral and cellular immune responses to heterologous (nonplasmodial) as well as plasmodial antigens. Previous studies have suggested that defects in macrophage function may be responsible for immunosuppression in malaria. In what way these cells might be altered in their immunoregulatory role during infection has not been clearly defined. One function of macrophages that is modified in malaria is the ability to secrete in vitro the monokine lymphocyte-activating factor (LAF). Adherent spleen cells obtained from mice early in Plasmodium berghei or P. yoelii infection secrete supernormal amounts of LAF. Adherent cells obtained later in infection show subnormal LAF-secreting activity and secrete an immunosuppressive substance. These modulations in macrophage function may be related to the quantity of parasite material ingested by these cells and might help explain the conversion of macrophages from a helper to a suppressor role in malaria.
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PMID:Cellular aspects of immunoregulation in malaria. 31 42

Among the unexplained changes caused by malaria in several host species, including man and mouse, are erythrophagocytosis and dyserythropoiesis. In order to see whether tumour necrosis factor (TNF) could contribute to these changes we injected recombinant human TNF intravenously into mice made very susceptible to this monokine by low density infection with a mouse malaria (Plasmodium vinckei) or prior injection of an extract of Coxiella burneti. Appreciable erythrophagocytosis, involving nucleated erythroblasts as well as mature red cells, was observed in bone marrow preparations from TNF-treated mice and those with severe illness due to P. vinckei, but in no other group. Dyserythropoiesis, involving irregularly-shaped nuclei and karyorrhexis, had the same distribution. TNF at concentrations up to 8 ng/ml was detected in the serum of all mice with severe malaria, but not uninfected animals or those with light infections. These findings are consistent with TNF making an important contribution to erythrophagocytosis and dyserythropoiesis, and thus to anaemia, in malaria and other conditions.
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PMID:Tumour necrosis factor may contribute to the anaemia of malaria by causing dyserythropoiesis and erythrophagocytosis. 317 31

The authors have earlier proposed that tumor necrosis factor (TNF) might contribute to the pathology of malaria. Here they report the outcome of injecting recombinant human TNF/cachectin into normal mice and others with low parasitemias (6-35%) of Plasmodium vinckei. The object was to see how precisely the pathologic features of the terminal stages of this infection could be produced, when parasitemias are 70-80%. Hypoglycemia, mid-zonal liver damage, and pulmonary accumulation of neutrophils in the pulmonary vasculature, all of which are seen in severe P vinckei infection, occurred within 4-12 hours after the mildly infected mice received TNF/cachectin. Uninfected mice were much less susceptible. TNF/cachectin also increases plasma lactate, a change seen in both the human and rodent diseases. From these findings and the recent literature on TNF/cachectin, including its detection in serum from malarial patients, it seems likely that excessive release of this monokine could account for certain of the unexplained pathologic features of human malaria.
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PMID:Possible roles of tumor necrosis factor in the pathology of malaria. 366 78

Serum from mice infected with Babesia microti or Plasmodium vinckei petteri and given lipopolysaccharide (LPS) contained appreciable amounts of tumour necrosis factor (TNF) and lymphocyte-activating factor (LAF; Interleukin I) activity. These monokines were not noted in serum from uninfected mice given the same dose of LPS. This pattern was repeated when adherent peritoneal cells from normal or infected mice were exposed to LPS in vitro and the supernatants assayed for LAF. This indicates that the hyper-reactivity of malaria and Babesia-infected mice to LPS resides in their macrophages, and that infection with these haemoprotozoa provides the host's macrophages with the same priming stimulus for subsequent triggering of monokine release as does an injection of Bacillus Calmette Guerin.
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PMID:Macrophages from Babesia and malaria infected mice are primed for monokine release. 633 93

The chemokines are a superfamily of small proteins secreted primarily by leukocytes and related by a conserved four-cystein motif. In the present study we investigated the serum levels of macrophage inflammatory protein 1 alpha (MIP-1 alpha) and interleukin-8 (IL-8). MIP-1 alpha is a neutrophil chemotactic protein important in acute and chronic inflammation. Recent studies demonstrated that MIP-1 alpha may also act as potent inhibitor of hemopoetic stem cell proliferation, which may be important in the development of prolonged anemia in patients suffering from Plasmodium falciparum malaria. IL-8 serum concentrations correlate with severity and outcome of infectious diseases. Moreover, recent reports indicate that IL-8 plays a major role in fatal gram-negative sepsis. It was the aim of this study to investigate the time course of MIP-1 alpha and IL-8 concentrations in patients suffering from acute P. falciparum infection. Blood samples of 20 patients suffering from severe P. falciparum malaria were investigated. MIP-1 alpha and IL-8 concentrations were determined using ELISA technique at admission, on Days 7, 14, 21, and 28. Maximal concentrations of MIP-1 alpha and IL-8 were found on Day 14, at a time when parasites were not detected in the smears. The serum levels of IL-8 on the day of admission were correlated to the parasite count. No correlation was seen between the hematokrit values and the MIP-1 alpha concentrations at any time.
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PMID:Serum concentrations of MIP-1 alpha and interleukin-8 in patients suffering from acute Plasmodium falciparum malaria. 760 66

Tumour necrosis factor (TNF) plays a pivotal role in the induction of cerebral complications during Plasmodium falciparum malaria. TNF secretion by macrophages can be induced by lipopolysaccharide (LPS) and by P. falciparum antigens, but it is unclear whether similar mechanisms control the monokine expression in both cases. The signal transduction pathway by which parasite antigens induce TNF secretion remains to be established. The results reported here, using various inhibitors of second messenger pathways, clearly demonstrate that the signal transduction leading to TNF secretion is mediated partly through protein kinase C and calmodulin-dependent protein kinase activation. Furthermore, this signal seems to be differentially regulated after LPS or parasite stimulation, since cyclo-oxygenase inhibition by indomethacin resulted in twofold more TNF production enhancement with LPS stimulation than with parasite stimulation. The nature of the receptor involved in the parasite induced-macrophage stimulation remains obscure. However, the results discussed here indicate that parasite antigens stimulate multiple signal transduction pathways via G protein. Identification of the different pathways involved in these receptor-mediated events may be invaluable in the development of specific inhibitors against TNF over-production during cerebral malaria.
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PMID:Signal transduction pathways involved in tumour necrosis factor secretion by Plasmodium falciparum-stimulated human monocytes. 782 69

We show that high levels of tumor necrosis factor-alpha (TNF-alpha) activity were consistently detected when monocytes were cocultured with Plasmodium falciparum schizont stage-parasitized erythrocytes that subsequently ruptured. Isolated pigment recovered from ruptured schizonts was found to specifically induce monocyte release of high levels of TNF-alpha and interleukin-1 beta (IL-1 beta). Particulate free-culture supernatant that contained various soluble parasite macromolecules induced relatively low levels of TNF-alpha and IL-1 beta. When isolated pigment was treated with protease, the monokine inducing-activity was abolished. Isolated pigment prepared from different natural isolates of P. falciparum stimulated variable levels of monokine production. We propose that in vivo, malaria pigment from parasites sequestered in the host microvasculature is a physiologically relevant moiety that interacts with monocytes and stimulates the release of TNF-alpha and IL-1 beta. These observations suggest that malaria pigment may be a virulence factor in the monokine-mediated induction of organ-specific and systemic pathophysiology in falciparum malaria.
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PMID:Plasmodium falciparum pigment induces monocytes to release high levels of tumor necrosis factor-alpha and interleukin-1 beta. 794 69

Chemokines are small pro-inflammatory peptides that are best known for their leukocyte-chemoattractant activity. The cloned leukocyte chemokine receptors, interleukin 8 receptor (IL-8R) types A and B and the macrophage inflammatory protein 1 alpha (MIP-1 alpha)/RANTES receptor, are related by sequence and chemokine binding to two herpesvirus products, and to the Duffy antigen that mediates erythrocyte invasion by the malaria-causing parasite Plasmodium vivax. Here, Sunil Ahuja, Ji-Liang Gao and Philip Murphy suggest that, in addition to the activation of leukocytes, chemokines may be important in the function of erythrocytes and, through molecular mimicry, in microbial pathogenesis.
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PMID:Chemokine receptors and molecular mimicry. 806 75

The Duffy Antigen Receptor for Chemokines (DARC) belongs to a family of erythrocyte chemokine receptors that bind C-X-C and C-C chemokines such as interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1) and regulated-on-activation, normal T cell-expressed and -secreted (RANTES), but not macrophage inflammatory protein 1 alpha (MIP-1 alpha) or MIP-1 beta. DARC has also been identified to a receptor for malaria parasites Plasmodium vivax and Plasmodium knowlesi. In the present study, we show that HIV-1 binds to RBCs from Caucasian individuals via DARC making RBCs able to transmit HIV to peripheral blood mononuclear cells (PBMCs). Furthermore, binding of HIV-1 particles to RBCs is inhibited by treating these cells with recombinant RANTES, but not with recombinant MIP-1 alpha prior to their incubation with HIV-1. This finding suggests that RBCs may function as a reservoir for HIV-1 or as a receptor for the entry of HIV-1 into CD4-cell subsets as well as neurons or endothelial cells.
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PMID:Binding of HIV-1 to RBCs involves the Duffy antigen receptors for chemokines (DARC). 992 12

To investigate the role of neutrophils in experimental cerebral malaria (ECM), in a previous study we found that early neutrophil depletion prevented the development of ECM and down regulated the expression of Th1 cytokines in the brain. To further clarify the mechanisms responsible for these findings, in the present study, using RT-PCR, we examined the expression of cytokine and chemokine mRNAs in neutrophils and macrophages after PbA infection. We found that, after infection, neutrophils not only expressed cytokines IL-2, IL-12p40, IL-18, IFN-gamma and TNF-alpha mRNAs, but also mRNAs for Th1 chemoattractive chemokines, monokine-induced by IFN-gamma (MIG), macrophage-inflammatory protein-1alpha (MIP-1alpha) and IFN-gamma inducible protein-10 (IP-10). Neutrophil depletion down regulated the expression of IL-18 and MIG mRNAs in macrophages, but did not affect the expression of IFN-gamma, TNF-alpha, MIP-1alpha and IP-10 mRNAs. Therefore, this study confirms our hypothesis that neutrophils may play a role in the pathogenesis of ECM via their expression of cytokines or chemokines.
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PMID:Cytokine and chemokine mRNA expression in neutrophils from CBA/NSlc mice infected with Plasmodium berghei ANKA that induces experimental cerebral malaria. 1143 37


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