title: Multifaceted Role of Heme during Severe Plasmodium falciparum Infections in India.
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.
authors.affiliation: Centre for Infection and Immunity of Lille, INSERM U1019, CNRS UMR 8204, Université Lille Nord de France, Institut Pasteur de Lille, Lille, France.
authors.forename: Esther
authors.initials: E
authors.lastname: Dalko
authors.affiliation: SCB Medical College, Cuttack, Odisha, India.
authors.forename: Bidyut
authors.initials: B
authors.lastname: Das
authors.affiliation: Centre for Infection and Immunity of Lille, INSERM U1019, CNRS UMR 8204, Université Lille Nord de France, Institut Pasteur de Lille, Lille, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Herbert
authors.affiliation: Instituto Gulbenkian de Ciencia, Oeiras, Portugal.
authors.forename: Constantin
authors.initials: C
authors.lastname: Fesel
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.
authors.forename: Sulabha
authors.initials: S
authors.lastname: Pathak
authors.affiliation: SCB Medical College, Cuttack, Odisha, India.
authors.forename: Rina
authors.initials: R
authors.lastname: Tripathy
authors.affiliation: 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.
authors.forename: Pierre-André
authors.initials: PA
authors.lastname: Cazenave
authors.affiliation: Institute of Life Sciences, Bhubaneswar, Odisha, India.
authors.forename: Balachandran
authors.initials: B
authors.lastname: Ravindran
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.
authors.forename: Shobhona
authors.initials: S
authors.lastname: Sharma
authors.affiliation: 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.
authors.forename: Sylviane
authors.identifier: http://orcid.org/0000-0003-0642-1423
authors.initials: S
authors.lastname: Pied
mesh_terms: D000328:Adult; D018932:Chemokine CCL2 / Q000097:blood; D018450:Disease Progression; D005260:Female; D006418:Heme / Q000378:metabolism*; D006466:Hemopexin / Q000378:metabolism; D006801:Humans; D007194:India; D016753:Interleukin-10 / Q000097:blood; D016778:Malaria, Falciparum / Q000097:blood* / Q000469:parasitology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D006418:Heme; D006466:Hemopexin