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)

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

The frequency of P. falciparum-specific interleukin (IL)-2-, interferon (IFN)-gamma-, tumor necrosis factor (TNF)-alpha- and IL-10-expressing CD3+ cells was studied in healthy Gabonese children segregated according to their clinical presentation at admission to a longitudinal study of severe and mild malaria. The percentage of IL-2- and TNF-alpha- expressing P. falciparum-specific CD3+ cells was significantly higher in the children with prior mild malaria and less frequent reinfections compared to the children with prior severe malaria and more frequent reinfections. No differences were shown for P. falciparum-specific IFN-gamma and IL-10 expression within CD3+ cells and parasite-non-specific expression of IL-2, IL-4, IL-6, IL-10, IL-13, TNF-alpha, and IFN-gamma within the CD4+, CD8+, TCRgamma\delta+ CD3+ and CD94+ CD3- cell populations, indicating that immunological determinants regulating the susceptibility to malaria in age-matched children are parasite-specific. The ability of P. falciparum-specific T cells to mount a rapid IL-2 and TNF-alpha response might be of significance in preventing severe disease and reinfection.
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PMID:Plasmodium falciparum-specific interleukin-2 and tumor necrosis factor-alpha expressing-T cells are associated with resistance to reinfection and severe malaria in healthy African children. 1554 42

The malaria parasite pigment hemozoin (Hz) is internalized by circulating and resident phagocytes and modulates their functions. We report here that Hz from Plasmodium falciparum inhibits proliferative responses of PHA stimulated human peripheral blood mononuclear cells (PBMC) in a dose dependent manner. Hz phagocytosed monocyte/macrophages (MO/MQ) secreted high levels of IL-10, IL-1beta and TNF-alpha, but inhibition of proliferation was mediated by IL-10 alone which was reversed by neutralization of the cytokine. Drastic decrease in the levels of IL-2, IL-12 and IFN-gamma were observed in supernatants from PBMC stimulated in the presence of Hz loaded MO/MQ cells. Exogenous addition of these cytokines did not abrogate immunosuppression indicating the inability of these cytokines to enhance proliferation in the presence of IL-10. We provide additional data that the IL-10 levels correlated positively with the load of Hz in the MO/MQ. Kinetics of IL-10 secretion analyzed up to day 6 in MO/MQ cultures fed with Hz revealed that high levels of IL-10 were secreted during the first 48 h after ingestion and decreased drastically at later time points.
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PMID:Modulation of cytokine profiles by malaria pigment--hemozoin: role of IL-10 in suppression of proliferative responses of mitogen stimulated human PBMC. 1556 49

Prenatal immunity to Plasmodium falciparum merozoite proteins involved in erythrocyte invasion may contribute to the partial protection against malaria that is acquired during infancy in areas of stable malaria transmission. We examined newborn and maternal cytokine and antibody responses to merozoite surface protein-1 (MSP-1), ribosomal phosphoprotein P0 (PfP0), and region II of erythrocyte binding antigen-175 (EBA-175) in infant-mother pairs in Kenya. Overall, 82 of 167 (50%), 106 of 176 (60%), and 38 of 84 (45%) cord blood lymphocytes (CBL) from newborns produced one or more cytokines in response to MSP-1, PfP0, and EBA-175, respectively. Newborns of primigravid and/or malaria-infected women were more likely to have antigen-responsive CBL than were newborns of multigravid and/or uninfected women at delivery. Newborn cytokine responses did not match those of their mothers and fell into three distinct categories, Th1 (21 of 55 CBL donors produced only gamma interferon and/or interleukin 2 [IL-2]), Th2 (21 of 55 produced only IL-5 and/or IL-13), and mixed Th1/Th2 (13 of 55). Newborns produced more IL-10 than adults. High and low levels of cord blood IL-12 p70 production induced by anti-CD40 activation were associated with malaria-specific Th1 and Th2 responses, respectively. Antigen-responsive CBL in some newborns were detected only after depletion of IL-10-secreting CD8 cells with enrichment for CD4 cells. These data indicate that prenatal sensitization to blood-stage Plasmodium falciparum occurs frequently in areas where malaria is holoendemic. Modulation of this immunity, possibly by maternal parity and malaria, may affect the acquisition of protective immunity against malaria during infancy.
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PMID:Distinct Th1- and Th2-Type prenatal cytokine responses to Plasmodium falciparum erythrocyte invasion ligands. 1590 75

We describe a novel method to screen malaria DNA vaccine candidates using a full-length cDNA library and a murine malaria infection model. For the development of effective malaria vaccines, much effort has been made with meager success. The completion of genome sequencing of Plasmodium falciparum has provided invaluable information for achieving this goal. We have been studying full-length cDNA libraries of malaria parasites as a part of genome analysis. Mice vaccinated with a DNA vaccine consisting of 2000 pooled clones showed significantly prolonged survival after challenge infection. In addition, spleen cells of vaccinated mice produced augmented levels of IL-2 and IFN-gamma when incubated with the crude parasite antigens, indicating that cellular immunity plays an important role in the protection. This approach will not only form the basis for development of malaria vaccines but will also be applicable to other parasites and pathogenic microorganisms.
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PMID:A novel method for development of malaria vaccines using full-length cDNA libraries. 1600 45

Individuals living in malaria-endemic areas show generally low T cell responses to malaria Ags. In this study, we show murine dendritic cell (DC) interaction with parasitized erythrocytes (pRBC) arrested their maturation, resulting in impaired ability to stimulate naive, but not recall T cell responses in vitro and in vivo. Moreover, within the naive T cell population, pRBC-treated DC were selectively deficient in priming CD8(+) but not CD4(+) T cells. Indeed, DC that had taken up pRBC were shown for the first time to efficiently prime CD4(+) T cell responses to a known protective merozoite Ag, MSP4/5. In contrast, impaired priming resulted in decreases in both proliferation and cytokine production by CD8(+) T cells. Deficient priming was observed to both a model and a Plasmodium berghei-specific CD8(+) T cell epitope. The mechanisms underlying the inability of parasite-treated DC to prime CD8(+) T cells were explored. pRBC treatment of DC from wild-type C57BL/6, but not from IL-10 knockout animals, suppressed DC-mediated T cell priming across a Transwell, suggesting active IL-10-dependent suppression. CD8(+) T cells were arrested at the G(0) stage of the cell cycle after two cell divisions post-Ag stimulation. The proliferation arrest was partially reversible by the addition of IL-2 or IL-7 to responder cultures. These results suggest that in malaria-endemic areas, priming of CD8(+) T cell responses may be more difficult to induce via vaccination than the priming of CD4(+) T cells. Moreover, pathogens may selectively target the CD8(+) T cell arm of protective immunity for immune evasion.
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PMID:Selectively impaired CD8+ but not CD4+ T cell cycle arrest during priming as a consequence of dendritic cell interaction with plasmodium-infected red cells. 1614 95

The Plasmodium yoelii nigeriensis murine model was used to evaluate the potential of liposome entrapped soluble blood stage antigens (sAg) based vaccine against malaria infection in BALB/c mice. Results from the present study revealed that immunization with E. coli lipid liposome (escheriosome) entrapped sAg provided strong protective immune responses that successfully suppressed drug resistant strain of Plasmodium yoelii, whereas other forms of sAg such as, egg PC/Chol liposomes entrapped, or its emulsion form with incomplete Freund's adjuvant (IFA) failed to impart significant level of protection. The immune responses, involved with escheriosome-sAg protection, were found to be associated with enhanced antigen specific CD4(+) and CD8(+) T-cell populations. Analysis of cytokine profiles in immunized animals revealed that the protective response was associated with the induction of a Th-1 (IL-2 and IFN-gamma) cells. Furthermore, vaccination with escheriosome entrapped sAg elicited high IgGl and IgG2a isotype response that played important role in imparting protection against blood stage infection of Plasmodium yoelii (MDR) in BALB/c mice.
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PMID:Escheriosome entrapped soluble blood stage antigens impart protective immunity against a multi-drug resistant isolate of Plasmodium yoelii nigeriensis in BALB/c mice. 1616 27

We aimed to investigate the relationship between quantitative Plasmodium vivax parasitaemia and serum cytokine levels in a highly endemic region of Turkey, where such a relation has not been investigated before. Active screening was done in a total of 1316 people residing in 33 villages of Sanliurfa province, Turkey. The study population consisted of 79 consecutive patients with P. vivax malaria, and a control group included 89 healthy subjects. Thick blood smears were examined for malaria parasite and parasite count. Serum samples were analysed for IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10 and IL-12 by the ELISA method. Compared to controls, levels of pro-inflammatory cytokines, i.e. IL-1beta, IL-6 and IL-12, were significantly higher in patients with parasitaemia. There was a significant positive correlation between serum IL-10 and IL-12 levels and the parasite burden (r = 0.264, P = 0.024 and r = 0.264, P = 0.024, respectively). Serum IL-8 levels showed a significant negative correlation with parasite burden (r =-0.356, P = 0.002). There was a positive correlation between IL-8 levels and age, while the opposite was observed for IL-12. High fever was correlated with IL-6 and IL-10 levels. Compared to controls, patients with a parasite count greater than 5000/microL had a significantly higher IL-1beta and IL-10 levels (P < 0.05), while the difference was not significant for patients with a parasite count less than 1000/microL. Thus, we can conclude that pro-inflammatory response against P. vivax gains more importance during periods of increased parasite burden.
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PMID:Parasite density and serum cytokine levels in Plasmodium vivax malaria in Turkey. 1662 5

We investigated the role of interferon (IFN)- gamma , interleukin (IL)-1 beta , IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)- alpha , and transforming growth factor (TGF)- beta in clinically well-defined groups of Plasmodium falciparum-infected patients manifesting mild malaria (MM), severe noncerebral malaria (SM), or cerebral malaria (CM) and in control subjects from Gondia, a malaria-endemic site in India, as well as in healthy subjects from non-malaria-endemic areas. Two-way coupled cluster analysis revealed 2 clusters of cytokines relevant to clinical subgroups of disease. The first cluster was composed of IFN- gamma , IL-2, IL-5, IL-6, and IL-12, the levels of which were significantly increased during infection but were predominant in patients with MM and allowed us to distinguish them from patients with SM or CM. The second cluster was composed of TGF- beta , TNF- alpha , IL-10, and IL-1 beta , the levels of which were highly correlated with each other in the different clinical groups of patients and significantly increased with disease severity, particularly in CM. Discriminant analyses allowed us to propose a minimal model. Levels of cytokines such as IL-5, IL-1 beta , IL-10, and IL-2 increase with infection. Levels of IL-12, IL-5, and IL-6 discriminate severe forms of malaria from MM. Finally, levels of IL-1 beta , IL-12, and IFN- gamma are relevant for the discrimination of CM from SM: high IL-1 beta levels are associated with CM, and high IL-12 and IFN- gamma levels are associated with SM.
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PMID:Clusters of cytokines determine malaria severity in Plasmodium falciparum-infected patients from endemic areas of Central India. 1677 26


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