Transforming Growth Factor β-Induced Failure of Resistance to Infection with Blood-Stage<i>Plasmodium chabaudi</i>in Mice

Tsutsui, Naohisa; Kamiyama, Tsuneo

doi:10.1128/iai.67.5.2306-2311.1999

Cited by 44 publications

(9 citation statements)

References 42 publications

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“…This observation, together with an earlier report that induction of NOS by stimulated hepatocytes prevented the development of parasites in hepatocytes, suggests that iNOS may be important in the liver of immune mice (27). Contrary to this theory are reports that iNOS activity remains largely unchanged throughout lethal P. berghei ANKA and non-lethal P. vinckei prtteri infections (32) or is undetectable in mice infected with P. c. chabaudi AS (35).…”

Section: Figurementioning

confidence: 76%

Expression of inducible nitric oxide synthase (iNOS) mRNA in target organs of lethal and non‐lethal strains of murine malaria

Nahrevanian

Dascombe

2002

Parasite Immunology

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Nitric oxide (NO) is a putative mediator of the immunological and/or pathological responses to malaria, consequently it is a potential target for novel drug therapy. Numerous cell types increase expression of inducible nitric oxide synthase (iNOS) under inflammatory conditions, the most relevant stimuli being cytokines and endotoxins. In this study the expression of iNOS mRNA in several target organs (brain, liver, spleen) of malaria have been investigated in MF1 mice during lethal Plasmodium (P.) berghei and non-lethal P. c. chabaudi infection. In P. berghei malaria, iNOS mRNA decreased in liver and was unchanged in spleen during the period of rising parasitaemia, but increased in both organs late in the infection, when parasitaemia was high and death imminent. In mice infected with P. c. chabaudi, spleen iNOS mRNA increased progressively throughout the early, peak and recovery periods of parasitaemia, but decreased in liver. Brain iNOS mRNA decreased in samples collected throughout the time courses of both infections. Hence it is evident that changes in iNOS mRNA in murine malaria depend upon the tissue, day of infection, degree of parasitaemia and strain of Plasmodium. These data indicate induction of iNOS mRNA in the spleen has a role in combating these strains of Plasmodium in MF1 mice. Failure to clear lethal P. berghei parasitaemia was associated with increased iNOS mRNA expression in the liver, which may contribute to the pathology of this malaria.

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Section: Figurementioning

confidence: 76%

Expression of inducible nitric oxide synthase (iNOS) mRNA in target organs of lethal and non‐lethal strains of murine malaria

Nahrevanian

Dascombe

2002

Parasite Immunology

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“…Neutralization of TGF‐ β leads to 100% mortality in BALB/c mice infected with normally nonlethal P. chabaudi A/J [60] and exacerbates pathology and accelerates mortality in IL‐10 –/– C57BL/6 mice (Li, Omer, Riley and Langhorne, unpublished observation). However, in some mouse‐parasite combinations, a very early burst of TGF‐ β production (within the first 24 h of infection) totally suppresses the inflammatory cytokine response leading to more rapid parasite growth and early death from anaemia (Omer, de Souza and Riley, unpublished observation); administration of high doses of exogenous TGF‐ β has similar effects [61]. Thus, the timing of the TGF‐ β (and IL‐10) response seems to be critical, with high levels too early in infection compromising cell‐mediated effector mechanisms and low levels later in infection leading to a failure to control the inflammatory cytokine cascade with subsequent development of severe pathology.…”

Section: Resolving Inflammationmentioning

confidence: 99%

The war between the malaria parasite and the immune system: immunity, immunoregulation and immunopathology

Artavanis‐Tsakonas

Tongren

Riley

2003

Clinical and Experimental Immunology

309

245

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SUMMARYThroughout history malaria has proved to be a significant threat to human health. Between 300 and 500 million clinical cases occur each year worldwide, approximately 2 million of which are fatal, primarily in children. The vast majority of malaria-related deaths are due to infection with Plasmodium falciparum ; P. vivax causes severe febrile illness but is rarely fatal. Following repeated exposure to infection, people living in malaria endemic areas gradually acquire mechanisms to limit the inflammatory response to the parasite that causes the acute febrile symptoms (clinical immunity) as well as mechanisms to kill parasites or inhibit parasite replication (antiparasite immunity). Children, who have yet to develop protective immune mechanisms are thus at greater risk of clinical malaria, severe disease and death than adults. However, two epidemiological observations indicate that this is, perhaps, an oversimplified model. Firstly, cerebral malaria -a common manifestation of severe malaria -typically occurs in children who have already acquired a significant degree of antimalarial immunity, as evidenced by lower mean parasite densities and resistance to severe anaemia. One potential explanation is that cerebral malaria is, in part, an immune-mediated disease in which immunological priming occurs during first infection, eventually leading to immunopathology on re-infection. Secondly, among travelers from nonendemic areas, severe malaria is more common -and death rates are higher -in adults than in children. If severe malaria is an immune-mediated disease, what might be priming the immune system of adults from nonendemic areas to cause immunopathology during their first malaria infection, and how do adults from endemic areas avoid severe immunopathology? In this review we consider the role of innate and adaptive immune responses in terms of (i) protection from clinical malaria (ii) their potential role in immunopathology and (iii) the subsequent development of clinical immunity. We conclude by proposing a model of antimalarial immunity which integrates both the immunological and epidemiological data collected to date. Keywords parasitic-protozoa human malaria immunoregulation ANTI-MALARIAL EFFECTOR MECHANISMSAs many of the surface antigens of malaria parasites and the parasite proteins inserted into the plasma membrane of the infected red blood cell are polymorphic or exhibit clonal antigenic variation, it has been proposed that one may need to develop a diverse repertoire of antibodies capable of blocking parasite invasion and tissue adhesion in order to attain effective antiparasite immunity [1]. For example, P. falciparum erythrocyte membrane protein 1 (PfEMP1), an antigen involved in parasite sequestration [2] and possibly pathogenesis of cerebral malaria (CM) [3], is encoded by a family of var genes which undergo frequent nonhomologous recombination leading to heterologous expression of antigenic variants by different parasites. Infection with a parasite variant that is not recognized by the existing an...

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“…Following emergence of parasites from the liver, malaria infection is characterized by an early phase of logarithmic replication of Plasmodium in circulating red blood cells. Compelling data in a murine model of malaria suggest that TGF-b and Tregs are central regulators of immunopathology and parasite expansion (34,(47)(48)(49)(50). In a recent study, Walther et al (41) have shown that following experimental malaria infection of human volunteers, enhanced TGF-b and Foxp3 + Treg responses in PBMCs correlated with a faster parasitic growth rate.…”

Section: Parasites Can Create a Cytokine Milieu Favoring Tregsmentioning

confidence: 99%

Section: Manipulation Of Natural Tregs By Parasitesmentioning

confidence: 99%

Natural regulatory T cells and parasites: a common quest for host homeostasis

Belkaid

Blank

Suffia

2006

Immunological Reviews

121

104

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This review discusses the roles played by natural CD4+ CD25+ regulatory T cells (natural Tregs) during parasitic infections. Natural Tregs may limit the magnitude of effector responses, which may result in failure to adequately control infection. However, natural Tregs also help to limit collateral tissue damage caused by vigorous antimicrobial immune responses. We discuss the hypothesis that parasites have evolved means to manipulate the host's natural Treg population, thereby generating conditions that secure survival in their vertebrate host for an extended period of time.

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Transforming Growth Factor β-Induced Failure of Resistance to Infection with Blood-StagePlasmodium chabaudiin Mice

Cited by 44 publications

References 42 publications

Expression of inducible nitric oxide synthase (iNOS) mRNA in target organs of lethal and non‐lethal strains of murine malaria

Expression of inducible nitric oxide synthase (iNOS) mRNA in target organs of lethal and non‐lethal strains of murine malaria

The war between the malaria parasite and the immune system: immunity, immunoregulation and immunopathology

Natural regulatory T cells and parasites: a common quest for host homeostasis

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