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Infect Immun. 2015 Oct;83(10):3793-9. doi: 10.1128/IAI.00531-15. Epub 2015 Jul 13.

Multifaceted Role of Heme during Severe Plasmodium falciparum Infections in India.

Author information

1
Centre for Infection and Immunity of Lille, INSERM U1019, CNRS UMR 8204, Université Lille Nord de France, Institut Pasteur de Lille, Lille, France.
2
SCB Medical College, Cuttack, Odisha, India.
3
Instituto Gulbenkian de Ciencia, Oeiras, Portugal.
4
Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.
5
Centre for Infection and Immunity of Lille, INSERM U1019, CNRS UMR 8204, Université Lille Nord de France, Institut Pasteur de Lille, Lille, France Immunologie-Immunopathologie-Immunothérapie, UPMC/CNRS UMR 7211, Paris, France.
6
Institute of Life Sciences, Bhubaneswar, Odisha, India.
7
Centre for Infection and Immunity of Lille, INSERM U1019, CNRS UMR 8204, Université Lille Nord de France, Institut Pasteur de Lille, Lille, France sylviane.pied@pasteur-lille.fr.

Abstract

Several immunomodulatory factors are involved in malaria pathogenesis. Among them, heme has been shown to play a role in the pathophysiology of severe malaria in rodents, but its role in human severe malaria remains unclear. Circulating levels of total heme and its main scavenger, hemopexin, along with cytokine/chemokine levels and biological parameters, including hemoglobin and creatinine levels, as well as transaminase activities, were measured in the plasma of 237 Plasmodium falciparum-infected patients living in the state of Odisha, India, where malaria is endemic. All patients were categorized into well-defined groups of mild malaria, cerebral malaria (CM), or severe noncerebral malaria, which included acute renal failure (ARF) and hepatopathy. Our results show a significant increase in total plasma heme levels with malaria severity, especially for CM and malarial ARF. Spearman rank correlation and canonical correlation analyses have shown a correlation between total heme, hemopexin, interleukin-10, tumor necrosis factor alpha, gamma interferon-induced protein 10 (IP-10), and monocyte chemotactic protein 1 (MCP-1) levels. In addition, canonical correlations revealed that heme, along with IP-10, was associated with the CM pathophysiology, whereas both IP-10 and MCP-1 together with heme discriminated ARF. Altogether, our data indicate that heme, in association with cytokines and chemokines, is involved in the pathophysiology of both CM and ARF but through different mechanisms.

PMID:
26169278
PMCID:
PMC4567638
DOI:
10.1128/IAI.00531-15
[Indexed for MEDLINE]
Free PMC Article

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