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

Natural killer T (NKT) cells are a unique population of lymphocytes that coexpress a semiinvariant T cell and natural killer cell receptors, which are particularly abundant in the liver. To investigate the possible effect of these cells on the development of the liver stages of malaria parasites, a glycolipid, alpha-galactosylceramide (alpha-GalCer), known to selectively activate Valpha14 NKT cells in the context of CD1d molecules, was administered to sporozoite-inoculated mice. The administration of alpha-GalCer resulted in rapid, strong antimalaria activity, inhibiting the development of the intrahepatocytic stages of the rodent malaria parasites Plasmodium yoelii and Plasmodium berghei. The antimalaria activity mediated by alpha-GalCer is stage-specific, since the course of blood-stage-induced infection was not inhibited by administration of this glycolipid. Furthermore, it was determined that IFN-gamma is essential for the antimalaria activity mediated by the glycolipid. Taken together, our results provide the clear evidence that NKT cells can mediate protection against an intracellular microbial infection.
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PMID:alpha -galactosylceramide-activated Valpha 14 natural killer T cells mediate protection against murine malaria. 1090 7

We previously reported that the major expanding lymphocytes were intermediate TCR (TCR(int)) cells (mainly NK1.1(-)) during malarial infection in mice. Cell transfer experiments of TCR(int) cells indicated that these T cells mediated resistance to malaria. However, TCR(int) cells always contain NK1.1(+)TCR(int) cells (i.e., NKT cells) and controversial results (NKT cells were effective or not for resistance to malaria) have been reported by different investigators. In this study, we used CD1d((-/-)) mice, which almost completely lack NKT cells in the liver and other immune organs. Parasitemia was prolonged in the blood of CD1d((-/-)) mice and the expansion of lymphocytes in the liver of these mice was more prominent after an injection of Plasmodium yoelii-infected erythrocytes. However, these mice finally recovered from malaria. In contrast to B6 mice, CD4(-)8(-) NKT cells as well as NK1.1(-)CD3(int) cells expanded in CD1d((-/-)) mice after malarial infection, instead of CD4(+) (and CD8(+)) NKT cells. These newly generated CD4(-)8(-)NKT cells in CD1d((-/-)) mice did not use an invariant chain of Valpha14Jalpha281 for TCRalpha. Other evidence was that severe thymic atrophy and autoantibody production were accompanied by malarial infection, irrespective of the mice used. These results suggest that both NK1.1(-) and NK1.1(+) subsets of TCR(int) cells (i.e., constituents of innate immunity) are associated with resistance to malaria and that an autoimmune-like state is induced during malarial infection.
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PMID:Resistance to malarial infection is achieved by the cooperation of NK1.1(+) and NK1.1(-) subsets of intermediate TCR cells which are constituents of innate immunity. 1159 Nov 13

Malaria, caused by infection with Plasmodium spp., is a life cycle-specific disease that includes liver injury at the erythrocyte stage of the parasite. In this study, we have investigated the mechanisms underlying Plasmodium berghei-induced liver injury, which is characterized by the presence of apoptotic and necrotic hepatocytes and dense infiltration of lymphocytes. Although both IL-12 and IL-18 serum levels were elevated after infection, IL-12-deficient, but not IL-18-deficient, mice were resistant to liver injury induced by P. berghei. Neither elevation of serum IL-12 levels nor liver injury was observed in mice deficient in myeloid differentiation factor 88 (MyD88), an adaptor molecule shared by Toll-like receptors (TLRs). These results demonstrated a requirement of the TLR-MyD88 pathway for induction of IL-12 production during P. berghei infection. Hepatic lymphocytes from P. berghei-infected wild-type mice lysed hepatocytes from both uninfected and infected mice. The hepatocytotoxic action of these cells was blocked by a perforin inhibitor but not by a neutralizing anti-Fas ligand Ab and was up-regulated by IL-12. Surprisingly, these cells killed hepatocytes in an MHC-unrestricted manner. However, CD1d-deficient mice that lack CD1d-restricted NK T cells, were susceptible to liver injury induced by P. berghei. Collectively, our results indicate that the liver injury induced by P. berghei infection of mice induces activation of the TLR-MyD88 signaling pathway which results in IL-12 production and activation of the perforin-dependent cytotoxic activities of MHC-unrestricted hepatic lymphocytes.
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PMID:Plasmodium berghei infection in mice induces liver injury by an IL-12- and toll-like receptor/myeloid differentiation factor 88-dependent mechanism. 1169 70

The important role played by CD8(+) T lymphocytes in the control of parasitic and viral infections, as well as tumor development, has raised the need for the development of adjuvants capable of enhancing cell-mediated immunity. It is well established that protective immunity against liver stages of malaria parasites is primarily mediated by CD8(+) T cells in mice. Activation of natural killer T (NKT) cells by the glycolipid ligand, alpha-galactosylceramide (alpha-GalCer), causes bystander activation of NK, B, CD4(+), and CD8(+) T cells. Our study shows that coadministration of alpha-GalCer with suboptimal doses of irradiated sporozoites or recombinant viruses expressing a malaria antigen greatly enhances the level of protective anti-malaria immunity in mice. We also show that coadministration of alpha-GalCer with various different immunogens strongly enhances antigen-specific CD8(+) T cell responses, and to a lesser degree, Th1-type responses. The adjuvant effects of alpha-GalCer require CD1d molecules, Valpha14 NKT cells, and interferon gamma. As alpha-GalCer stimulates both human and murine NKT cells, these findings should contribute to the design of more effective vaccines against malaria and other intracellular pathogens, as well as tumors.
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PMID:Natural killer T cell ligand alpha-galactosylceramide enhances protective immunity induced by malaria vaccines. 1187 90

Alfa-Galactosyl Ceramide was isolated from Ocean sponge which has antitumor effect against several tumors in in vivo animal model with no cytotoxicity. KRN7000(KRN) is the most potent alpha-Galactosyl Ceramide modified from the one isolated from Ocean sponge. KRN is also active against metastatic tumors through the activation ofanimal immune system. Research efforts in learning the mechanism of action, we found the important role of dendritic cells(DC) and NKT cells. NKT cells was first characterized in 1988 which is overlap some part with NK cells and T-Cells and majority is different from NK and T. KRN is active through the activation of DC and NKT in giving antigen specific immune stimulation in animal. This antigen specific stimulation is memorized by immune system and can reject second tumor challenge. KRN is not active in nude mice and NKT deficient animal. NKT cells level in blood is lower in patients with autoimmune disease, cancer, HIV positive or aplastic anemia. NKT rapidly releases IL-4 and IFN-gamma at high level when activated. NKT is CD1d and TCR restricted. NKT plays important role in autoimmune disease such as Type 1 Diabetes, Scleroderma and Systemic Lupus Erythematosus, infections such as Mycobacteria, Listeria and Malaria, GVHD control and tumor rejection. NKT acts as double edge sword, aggressive and suppressive ways. KRN can prevent the onset of Type 1 Diabetes, inhibit replication of hepatitis virus B in liver and suppress malaria replication in activating NKT cells. KRN can activate NKT through DC and activated NKT activates NK, T and macrophage. KRN also expands NKT cells and expanded NKT has full function. Although the exact role of DC and NKT is not clear, KRN clinical study results in conjunction with DC and NKT cell activation are expected.
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PMID:Role of NKT cells and alpha-galactosyl ceramide. 1243 Aug 64

NKT cells are specialized cells coexpressing NK and T cell receptors. Upon activation they rapidly produce high levels of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) and are therefore postulated to influence T(H)1/T(H)2 immune responses. The precise role of the CD1/NKT cell pathway in immune response to infection remains unclear. We show here that CD1d-restricted NKT cells from distinct genetic backgrounds differentially influence T(H)1/T(H)2 polarization, proinflammatory cytokine levels, pathogenesis, and fatality in the P. berghei ANKA/rodent model of cerebral malaria. The functional properties of CD1d-restricted NKT cells vary according to expression of loci of the natural killer complex (NKC) located on mouse chromosome 6, which is shown here to be a significant genetic determinant of murine malarial fatalities.
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PMID:Regulation of murine cerebral malaria pathogenesis by CD1d-restricted NKT cells and the natural killer complex. 1264 56

CD1d-restricted NKT cells are a novel T cell lineage with unusual features. They co-express some NK cell receptors and recognize glycolipid antigens through an invariant T cell receptor (TCR) in the context of CD1d molecules. Upon activation through the TCR, NKT cells produce large amounts of IFN-gamma and IL-4. It has been proposed that rapid cytokine output by activated NKT cells may induce bystander activation of other lymphoid lineages. The impact of CD1d-restricted NKT cell activation in the induction of B cell-mediated immune responses to infection is still unclear. We show here that CD1-restricted NKT cells contribute to malarial splenomegaly associated with expansion of the splenic B cell pool and enhance parasite-specific antibody formation in response to Plasmodium berghei infection. The increased B cell-mediated response correlates with the ability of NKT cells to promote Th2 immune responses. Additionally, antibody responses against the glycosylphosphatidylinositol (GPI)-anchored protein merozoite surface protein 1 (MSP-1) were found to be significantly lower in CD1(-/-) mice compared to wild-type animals. P. berghei-infected MHC class II (MHCII)(-/-) mice also generated antibodies against MSP-1, suggesting that antibody production against GPI-anchored antigens in response to malaria infection can arise from both MHCII-dependent and independent pathways.
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PMID:CD1d-restricted NKT cells contribute to malarial splenomegaly and enhance parasite-specific antibody responses. 1293 35

Inoculation with erythrocytes infected with Plasmodium berghei, a protozoan causing mouse lethal malaria, induces liver injury in mice, although the parasite cannot invade host hepatocytes at this infectious stage. As previously reported, hepatic infiltrates participate in this liver injury by exerting their perforin-dependent killing action. Here, we have investigated the cellular mechanisms underlying P. berghei-induced incidental liver injury. Hepatic lymphocytes from P. berghei-infected mice killed normal hepatocytes, but not ConA-induced lymphoblasts. Furthermore, the hepatic lymphocytes from infected C57BL/6 mice displayed cytotoxicity against hepatocytes from C57BL/6 and BALB/c mice, indicating MHC-unrestricted hepatocytotoxicity by these hepatic lymphocytes. NK cells were not involved in this hepatocytotoxicity. However, DX5+ cells sorted from the liver of infected CD1d-deficient mice killed normal hepatocytes, indicating that CD1d-independent DX5+ T cells are the effector cells. The hepatocytotoxicity of these hepatic DX5+ T cells did not require TCR engagement. These findings indicate that hepatic CD1d-independent DX5+ T cells play a critical role in P. berghei-induced liver injury. Our studies may have general implications for tissue injuries that are caused by 'bystander killing' or other poorly defined cell-mediated killing mechanisms.
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PMID:Contribution of CD1d-unrestricted hepatic DX5+ NKT cells to liver injury in Plasmodium berghei-parasitized erythrocyte-injected mice. 1509 77

This study reports the molecular characterization and tissue expression of the non-human Aotus nancymaae primate CD1b isoform in the search for an experimental animal model to be used in evaluating the role of non-peptide antigen-presentation molecules in the immune response to infectious agents. CD1b expression on the surface of A. nancymaae peripheral blood monocyte-derived dendritic cells, shown by flow cytometry, was made possible by using human CD1b isoform antibodies. Studying the expression of CD1b-encoded transcripts revealed this molecule's broad distribution in several tissues. The A. nancymaae CD1b transcript-encoded amino-acid sequence showed 95.5% identity with the human sequence. Such high sequence homology was reflected in the identical structural conservation of how pockets A', C' and F' and tunnel T' conforming the antigen's binding site are organized, the similar arrangement of those amino-acids interacting with the T-cell receptor (TCR) during antigen presentation, and the conservation of YQNI-motif sequence in the cytoplasmatic tail (responsible for the molecule's intracellular trafficking in humans). Comparing the structure of human CD1a and CD1b and mouse CD1d proteins with CD1b structure in A. nancymaae obtained by minimization revealed that changes in the latter molecule's alpha1 and alpha2 domains imposed a narrowing of the antigen-binding groove in A. nancymaae CD1b. The high structural similarity between A. nancymaae CD1b and that from humans presented in this study leads to A. nancymaae being proposed as a suitable experimental animal model for analyzing CD1b in vivo, mainly in bacterial and parasite infections such as tuberculosis and malaria, respectively.
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PMID:Identifying and structurally characterizing CD1b in Aotus nancymaae owl monkeys. 1536 47

The MHC class I-like CD1d glycoprotein is a member of the CD1 family of Ag-presenting molecules and is responsible for the selection of NKT cells. A number of ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells have been identified. These include glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules. The presentation of many of these molecules can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer or can be deleterious. This review will highlight these ligands in a discussion of their potential use against (and role in the pathogenesis of) these diseases.
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PMID:CD1d ligands: the good, the bad, and the ugly. 1681 29


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