Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we report that infection with Plasmodium yoelii 17XL, a lethal strain of rodent malaria, does not result in death in the DBA/2 strain of mice. In contrast to BALB/c mice, DBA/2 mice developed significantly less parasitemia and never manifested symptoms of cerebral malaria (CM) on infection with this parasite. Moreover, the histological changes evident in the brain of susceptible BALB/c were absent in DBA/2 mice. Interestingly, the resistant DBA/2 mice when treated with recombinant interleukin (IL)-2, were found to develop CM symptoms and the infection became fatal by 6 to 8 days after infection. This condition was associated with an augmented interferon-gamma and nitric oxide production. Unexpectedly, IL-10 levels were also elevated in IL-2-treated DBA/2 mice during late stage of infection (at day 6 of infection) whereas the inverse relationship between IL-10 and interferon-gamma or nitric oxide was maintained in the early stage of infection (at day 3 after infection). The level of tumor necrosis factor-alpha production was moderately increased in the late phase of infection in these mice. Histology of brain from IL-2-treated mice demonstrated the presence of parasitized erythrocytes and infiltration of lymphocytes in cerebral vessels, and also displayed some signs of endothelial degeneration. Confocal microscopical studies demonstrated preferential accumulation of gammadelta T cells in the cerebral vessels of IL-2-treated and -infected mice but not in mice treated with IL-2 alone. The cells recruited in the brain were activated because they demonstrated expression of CD25 (IL-2R) and CD54 (intercellular adhesion molecule 1) molecules. Administration of anti-gammadelta mAb prevented development of CM in IL-2-treated mice until day 18 after infection whereas mice treated with control antibody showed CM symptoms by day 6 after infection. The information concerning creating pathological sequelae and death in an otherwise resistant mouse strain provides an interesting focus for the burden of pathological attributes on death in an infectious disease.
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PMID:Cerebral malaria in mice: interleukin-2 treatment induces accumulation of gammadelta T cells in the brain and alters resistant mice to susceptible-like phenotype. 1114 89

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

The current vaccine against tuberculosis, Mycobacterium bovis strain bacillus Calmette-Guerin (BCG), offers potential advantages as a live, innately immunogenic vaccine vehicle for expression and delivery of protective recombinant antigens. Malaria is one of the severest parasitic diseases in humans especially in the developing world. No efficacious vaccine is currently available. However, circumsporozoite protein (CSP) is a malaria vaccine candidate currently undergoing clinical trials. We analyzed the immune response to recombinant BCG (rBCG) vaccine expressing Plasmodium falciparum CSP (BCG-CSP) under the control of heat shock protein 70 promoter in BALB/c mice. The lymphocytes proliferative response to P. falciparum soluble antigen was significantly higher than those in the groups of BCG and normal saline, and the production of cytokines (IFN-gamma and IL-2) in response to malaria antigen was significantly higher in rBCG and BCG groups than control group of normal saline. A specific IgG antibody response against P. falciparum antigen of CSP was also characterized. The booster injection could enhance the production of cytokine, proliferation responses of spleen lymphocytes and the antibodies titer of BCG-CSP. The results in the study demonstrated that rBCG vaccine producing CSP is an appropriate vaccine for further evaluation in non-human primates.
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PMID:Recombinant Mycobacterium bovis BCG producing the circumsporozoite protein of Plasmodium falciparum FCC-1/HN strain induces strong immune responses in BALB/c mice. 1188 Feb 22

A primary infection with Plasmodium chabaudi chabaudi (AS) is characterized by an expansion of gammadelta cells after the acute phase of infection in mice. This is particularly marked during chronic infections in B cell-deficient mice. Infections in gammadelta T cell-deficient mice suggest that, although these cells play some role in the control of parasitaemia and can produce interferon-gamma, they do not appear to be involved in the development of hypoglycaemia, loss of weight and temperature during a P. c. chabaudi infection. However, gammadelta T cells do influence the nature of the CD4+ T cell response during infection since, in their absence, Th2-like responses, such as interleukin (IL)-4 production and help for malaria-specific antibody responses, are more pronounced. This alteration in CD4+ T cells is reflected in a more rapid and greater immunoglobulin (Ig)G1 and IgG3 antibody response to the parasite. The large gammadelta T cell expansion normally observed in infected B cell-deficient mice did not take place in the absence of IL-2, and double-knockout mice lacking both B cells and functional IL-2 were highly susceptible to lethal infection with P. c. chabaudi. The majority of the single IL-2 knockout mice, in contrast, were able to control and clear a primary infection, suggesting that for the CD4+ T cell and antibody response, IL-2 could be replaced by other cytokines.
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PMID:The influence of gammadelta T cells on the CD4+ T cell and antibody response during a primary Plasmodium chabaudi chabaudi infection in mice. 1198 58

Fifty subjects living in a malaria endemic area were studied at diagnosis of a Plasmodium falciparum attack and 3 weeks later. Absolute numbers of CD3(+), CD4(+) and CD8(+) lymphocytes as well as plasma cytokines and secreted cytokines after in vitro mitogenic stimulation were measured. At enrollment, lymphopenia was observed, lending support to the reallocation hypothesis during the acute phase. A significant elevation of the number of CD8(+) cells was present in the peripheral blood during the recovery phase. During the acute phase, plasma IL-6 levels peaked while in vitro production capacity was high at both phases. Plasma IL-6 concentrations were positively related to blood parasite density at D0, as IL-4 and IFN-gamma, suggesting an early intervention of these cytokines. Plasma IL-2 levels were low at diagnosis although cells retained their ability to produce IL-2, which was found more frequently in plasma after cure. Acquisition of immunity with age was in relation with greater secretion abilities of cells for type 1 and type 2 cytokines during the parasite clearance phase. We conclude to an early implication of type 2 cytokines and IFN-gamma, with particularly high levels of IL-6.
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PMID:Plasma and in vitro levels of cytokines during and after a Plasmodium falciparum malaria attack in Gabon. 1220 92

beta Androstenes steroid up-regulates immunity to increase resistance against lethal infection and lethal radiation, and mediates a rapid recovery of hematopoietic precursor cells after radiation injury. beta Androstenetriol increases the levels of the TH(1) cytokines, IL-2, IL-3, IFN gamma and counteracts hydrocortisone mediated immune suppression. In contrast, 17 alpha androstenediol inhibits proliferation and mediates apoptosis in tumor cells of murine and human origin. Its epimer 17beta androstenediol does not. The antiproliferative functions of 17 alpha androstenediol are not dependent on either the estrogen or androgen receptors. Our findings show that beta androstenes and analogs protect the host from lethal infection by DNA or RNA viruses such as, herpesvirus type 2, coxsackievirus B4, influenza, and arthropod borne viruses. These androstenes also protected the host from lethal bacterial infections by Enterococcus faecalis, Pseudomonas aeruginosa, and Klebsiella pneumonia and from parasites infections, i.e. Cryptosporidium parvum, and malaria. In vivo, the level of potency follows the order: dehydroepiandrosterone<<<androstenediol<androstenetriol with the latter being up to one hundred thousand times more potent in protecting the host from infections than the first. In vitro, their effects are also dramatically different from one another with only beta androstenetriol potentiating the cellular response by increasing lymphocyte activation and counteracting hydrocortisone immune-suppressive activity. Conceptually, the androstenes form a new and different subclass of steroid hormones with unique physiological properties. Following host injury, the balance between the epimers and isomers is a determining factor in the overall regulation of hematopoiesis, TH(l)/TH(2) balance, and host resistance to infections and tumor growth.
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PMID:Immune up-regulation and tumor apoptosis by androstene steroids. 1239 92

Although there is good evidence that immunity to the blood stages of malaria parasites can be mediated by different effector components of the adaptive immune system, target antigens for a principal component, effector CD4(+) T cells, have never been defined. We generated CD4(+) T cell lines to fractions of native antigens from the blood stages of the rodent parasite, Plasmodium yoelii, and identified fraction-specific T cells that had a Th1 phenotype (producing IL-2, IFN-gamma, and tumor necrosis factor-alpha, but not IL-4, after antigenic stimulation). These T cells could inhibit parasite growth in recipient severe combined immunodeficient mice. N-terminal sequencing of the fraction showed identity with hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT). Recombinant HGXPRT from the human malaria parasite, Plasmodium falciparum, activated the T cells in vitro, and immunization of normal mice with recombinant HGXPRT reduced parasite growth rates in all mice after challenge.
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PMID:The purine salvage enzyme hypoxanthine guanine xanthine phosphoribosyl transferase is a major target antigen for cell-mediated immunity to malaria. 1259 31

Malaria infection has long been associated with diminished T cell responses in vitro and more recently in experimental studies in vivo. Suppression of T cell-proliferative responses during malaria has been attributed to macrophages in a variety of murine and human systems. More recently, however, attention has been directed at the role of dendritic cells in this phenomenon, with several studies suggesting that maturation of dendritic cells is inhibited in vitro by the presence of malaria-infected E. In the studies reported here, we have examined the function of dendritic cells taken directly from infected mice. We found that they express high levels of costimulatory proteins and class II MHC, can activate naive T cells to produce IL-2 as efficiently as dendritic cells from uninfected mice, and support high levels of IFN-gamma production by naive T cells through an IL-12-dependent mechanism. Dendritic cells from infected mice also support higher levels of TNF-alpha production by naive T cells. These same dendritic cells present parasite Ag to a malaria-specific T cell hybridoma, a finding that demonstrates that dendritic cells participate in the generation of Ag-specific immunity during infection. Our findings challenge the contention that dendritic cell function is inhibited by malaria infection.
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PMID:Dendritic cells from malaria-infected mice are fully functional APC. 1468 57

Cell-mediated immunity (CMI) may be important in immunity against blood-stage malaria. Accordingly, we examined the role of type 1 cytokines in the resolution of Plasmodium chabaudi adami malaria in mice genetically modified to have type 1 cytokine gene defects. Parasitemia was prolonged in double knockout (IL-2(-/-), IFNgamma(-/-)) mice compared to control mice. Despite deficiencies in gammadelta T cell and B cell subsets, these mice produced anti-malarial antibodies and eventually cured their infections, possibly by antibody-mediated immunity. However, because acute P. c. adami parasitemia may also be suppressed by CMI, the requirements for IL-2 and IFNgamma were evaluated in mice lacking B cells and functional IL-2 or IFNgamma genes. Acute malaria in J(H)(-/-), IL-2(-/-) mice was prolonged, but eventually cured. In contrast, J(H)(-/-), IFNgamma(-/-) mice developed unremitting parasitemia. These data strongly suggest that IFNgamma, but not IL-2, plays an essential role in the expression of CMI against P. c. adami infections. This finding may prove useful in developing malarial vaccines aimed at inducing CMI.
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PMID:Plasmodium chabaudi adami: interferon-gamma but not IL-2 is essential for the expression of cell-mediated immunity against blood-stage parasites in mice. 1496 93

Accumulating evidence indicates that platelets play a critical role in the pathogenesis of experimental severe malaria (ESM) elicited by infection with Plasmodium berghei. Mice injected on day 1 of P berghei infection (early) with either anti-CD41 or anti-CD61 monoclonal antibodies (mAbs) exhibited significantly (P<.001) increased survival from ESM compared with infection controls, indicating that platelets function early in the disease. In contrast, groups of mice treated on days 4, 5, and 6 (late) with anti-CD41 mAb exhibited similar mortality as controls. Because platelet depletion by anti-CD41 mAb on day 4 of infection did not protect mice, and platelet adherence occurs on day 6, platelet adherence to endothelium is not required to mediate malarial pathogenesis. Few platelet microparticles were detected in the blood during the course of malaria, but large numbers of erythrocyte vesicles, microparticles, and debris were detected. The protective effect of early anti-CD41 mAb treatment was independent of the number of platelets, platelet microparticles, erythrocyte-platelet conjugates, and erythrocyte vesicles. Mice treated early with anti-CD41 mAb exhibited markedly altered cytokine production on day 4 of P berghei infection (increased interleukin 10 [IL-10], IL-1alpha, IL-6, interferon-gamma [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]; decreased IL-2) but no decline in coagulation factors compared with rat immunoglobulin G (IgG)-treated controls, indicating that platelets regulate the levels of pathogenic cytokines.
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PMID:Platelet depletion by anti-CD41 (alphaIIb) mAb injection early but not late in the course of disease protects against Plasmodium berghei pathogenesis by altering the levels of pathogenic cytokines. 1549 26


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