High Levels of Inducible Nitric Oxide Synthase mRNA Are Associated with Increased Monocyte Counts in Blood and Have a Beneficial Role in<i>Plasmodium falciparum</i>Malaria

Chiwakata, Collins Batsirai; Hemmer, Christoph Josef; Dietrich, M.

doi:10.1128/iai.68.1.394-399.2000

Cited by 64 publications

(44 citation statements)

References 33 publications

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“…37 These genetic studies have led to similarly conflicting results as have biological observations, according to which nitric oxide (NO) was first identified as a potential cause of neurosuppression leading to cerebral malaria. 38 However, increased expression of NOS2 in PBMC, and particularly in monocytes, 39 leading to increased NOS2-derived NO synthesis, is associated with protection against clinical disease. 40 It seems therefore too early to establish a definitive causal association between NOS2 polymorphisms and malaria susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Human genetic factors related to susceptibility to mild malaria in Gabon

Migot-Nabias¹,

Mombo²,

Luty³

et al. 2000

Genes Immun

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Several human genetic factors, including red blood cell polymorphisms (ABO blood group, sickle-cell trait, G6PD deficiency) as well as point mutations in the mannose binding protein (MBP) and in the promoter regions of both the TNF-␣ and NOS2 genes, influence the severity of disease due to infection with Plasmodium falciparum. We assessed their impact on mild P. falciparum malaria, as part of a longitudinal investigation of clinical, parasitological and immunological parameters in a cohort of 300 Gabonese schoolchildren. We found the following frequencies: blood group O (0.54), sicklecell trait (0.23), G6PD deficiency (0.09), MBP gene mutations (0.34), TNF-␣ promoter mutations (at positions −238: 0.17 and −308: 0.22) and NOS2 promoter mutation (0.18). Blood group O or hemoglobin AA were associated with protection against higher parasitemia. Girls with normal G6PD enzyme activity were protected against clinical malaria attacks. In addition, we demonstrated for the first time that the mutation at position −238 of the gene coding for the promoter region of TNF-␣ was positively correlated with the level of the antibody response specific for epitopes of the antigens MSA-2 and RAP-1 of P. falciparum. Genes and Immunity (2000) 1, 435-441.

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Section: Discussionmentioning

confidence: 99%

Human genetic factors related to susceptibility to mild malaria in Gabon

Migot-Nabias¹,

Mombo²,

Luty³

et al. 2000

Genes Immun

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“…However, in contrast to our results, Chaudhuri et al (2008) reported a significant rise in the activity of SOD in infected dogs with B. gibsoni. Although, the mechanism of increased activity of SOD in infected erythrocytes cannot be explained explicity, it is likely that up-regulation of the synthesis of SOD is driven by the body's homeostatic mechanisms to counter oxidative damage due to parasitemia and multiplication of parasites inside the cells (Chiwakata et al 2000, Chaudhuri et al 2008. It may be associated with a high percentage of reticulocytes in the infected dogs because the activity of enzymes is higher in reticulocytes compared with mature erythrocytes (Yamasaki et al 2000, Otsuko et al 2001.…”

Section: Discussionmentioning

confidence: 99%

Status of lipid peroxidation and antioxidant enzymes in goats naturally infected with Babesia ovis

Esmaeilnejad

Tavassoli

Asri‐Rezaei

et al. 2012

Acta Parasitologica

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This study aimed to assess lipid peroxidation and antioxidant enzymes in goats naturally infected with Babesia ovis. Red blood cell count (RBC), hemoglobin (Hb) concentration, packed cell volume (PCV), malondialdehyde (MDA) concentration, erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities and total antioxidant capacity (TAC) were determined in 15 goats naturally infected with B. ovis as well as same number of healthy goats. The parasitological diagnosis was confirmed using polymerase chain reaction (PCR) analysis by amplifying a partial 18S rRNA gene sequence of B. ovis. Percentage of parasitemia varied from 0.01 to 1%. The activities of erythrocyte GSH-Px, SOD, CAT and TAC were significantly lower (p<0.05) in the infected goats than in healthy ones. MDA concentration in erythrocytes of infected goats was significantly higher in infected goats than in healthy ones (p<0.05). Severity of parasitemia showed a positive correlation with the MDA and negative correlation with PCV, SOD, CAT, GSH-Px and TAC. Also, MDA was negatively correlated with PCV, SOD, CAT, GSH-Px and TAC. The results of this study suggested that oxidative damage to RBCs may contribute to the pathogenesis of anemia in caprine babesiosis.

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“…This mechanism is also of importance for the understanding of immune defense mechanisms during human malaria. NO can be produced by human hepatocytes (35), and high iNOS expression from patients infected with P. falciparum correlates with a mild infection (9). Since the liver stage of P. berghei infection only lasts for 2 days, it may be of advantage to develop vaccines that increase liver-specific cell responses and do not induce IL-4 or IL-13.…”

Section: Discussionmentioning

confidence: 99%

Mice Deficient in Interleukin-4 (IL-4) or IL-4 Receptor α Have Higher Resistance to Sporozoite Infection withPlasmodium berghei(ANKA) than Do Naive Wild-Type Mice

Saeftel

Krueger²,

Arriens³

et al. 2004

Infect Immun

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BALB/c interleukin-4 (IL-4؊/؊ ) or IL-4 receptor-␣ (IL-4r␣ ؊/؊ ) knockout (KO) mice were used to assess the roles of the IL-4 and IL-13 pathways during infections with the blood or liver stages of plasmodium in murine malaria. Intraperitoneal infection with the blood-stage erythrocytes of Plasmodium berghei (ANKA) resulted in 100% mortality within 24 days in BALB/c mice, as well as in the mutant mouse strains. However, when infected intravenously with the sporozoite liver stage, 60 to 80% of IL-4 ؊/؊ and IL-4r␣ ؊/؊ mice survived, whereas all BALB/c mice succumbed with high parasitemia. Compared to infected BALB/c controls, the surviving KO mice showed increased NK cell numbers and expression of inducible nitric oxide synthase (iNOS) in the liver and were able to eliminate parasites early during infection. In vivo blockade of NO resulted in 100% mortality of sporozoite-infected KO mice. In vivo depletion of NK cells also resulted in 80 to 100% mortality, with a significant reduction in gamma interferon (IFN-␥) production in the liver. These results suggest that IFN-␥-producing NK cells are critical in host resistance against the sporozoite liver stage by inducing NO production, an effective killing effector molecule against Plasmodium. The absence of IL-4-mediated functions increases the protective innate immune mechanism identified above, which results in immunity against P. berghei infection in these mice, with no major role for IL-13.Both cell-mediated immunity and humoral immunity play important roles in the mechanisms of defense against human and animal malaria. These defense mechanisms largely depend on early innate responses and antigen-specific T helper (Th) cell activation. The importance of the Th1 cytokine gamma interferon (IFN-␥) for protection against malaria has been shown in murine models of malaria (1,11,47,50,54,55,57), with vaccinated animals lacking IFN-␥ showing greatly increased susceptibility, increased parasitemia, and a shorter life span.The role of nitric oxide (NO) in the defense against malaria infection seems to be dependent on the stage of the malaria parasite. In a blood-stage infection with Plasmodium berghei, it was shown that neither NO nor NK cells were important for the control of parasitemia (12, 55). In contrast, compared to the liver-phase stage of sporozoite infection, NK cells were shown to be activated by sporozoites (37) and produced IFN-␥ (31, 37). A clear role for NO as a defense mechanism against the liver stage of P. berghei was found only in vaccinated animals (25,36,45,48).Concerning Th2 response, it was shown that a lack of interleukin-4 (IL-4) in the murine infection with Plasmodium chabaudi chabaudi results in a course of infection similar to that seen in the wild-type mice (2, 50, 51), with slightly different parasitemia kinetics. Moreover the in vitro Th1 immune responses were sustained in the IL-4-deficient mice (51). All of these studies were done by infection of mice with parasitized erythrocytes, but no study has been performed that focused on the role of I...

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High Levels of Inducible Nitric Oxide Synthase mRNA Are Associated with Increased Monocyte Counts in Blood and Have a Beneficial Role inPlasmodium falciparumMalaria

Cited by 64 publications

References 33 publications

Human genetic factors related to susceptibility to mild malaria in Gabon

Human genetic factors related to susceptibility to mild malaria in Gabon

Status of lipid peroxidation and antioxidant enzymes in goats naturally infected with Babesia ovis

Mice Deficient in Interleukin-4 (IL-4) or IL-4 Receptor α Have Higher Resistance to Sporozoite Infection withPlasmodium berghei(ANKA) than Do Naive Wild-Type Mice

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