title: Evidence of IL-17, IP-10, and IL-10 involvement in multiple-organ dysfunction and IL-17 pathway in acute renal failure associated to Plasmodium falciparum malaria.
abstract: BACKGROUND
  Plasmodium falciparum malaria in India is characterized by high rates of severe disease, with multiple organ dysfunction (MOD)-mainly associated with acute renal failure (ARF)-and increased mortality. The objective of this study is to identify cytokine signatures differentiating severe malaria patients with MOD, cerebral malaria (CM), and cerebral malaria with MOD (CM-MOD) in India. We have previously shown that two cytokines clusters differentiated CM from mild malaria in Maharashtra. Hence, we also aimed to determine if these cytokines could discriminate malaria subphenotypes in Odisha.
  
  
  METHODS
  P. falciparum malaria patients from the SCB Medical College Cuttack in the Odisha state in India were enrolled along with three sets of controls: healthy individuals, patients with sepsis and encephalitis (n = 222). We determined plasma concentrations of pro- and anti-inflammatory cytokines and chemokines for all individuals using a multiplex assay. We then used an ensemble of statistical analytical methods to ascertain whether particular sets of cytokines/chemokines were predictors of severity or signatures of a disease category.
  
  
  RESULTS
  Of the 26 cytokines/chemokines tested, 19 increased significantly during malaria and clearly distinguished malaria patients from controls, as well as sepsis and encephalitis patients. High amounts of IL-17, IP-10, and IL-10 predicted MOD, decreased IL-17 and MIP-1α segregated CM-MOD from MOD, and increased IL-12p40 differentiated CM from CM-MOD. Most severe malaria patients with ARF exhibited high levels of IL-17.
  
  
  CONCLUSIONS
  We report distinct differences in cytokine production correlating with malarial disease severity in Odisha and Maharashtra populations in India. We show that CM, CM-MOD and MOD are clearly distinct malaria-associated pathologies. High amounts of IL-17, IP-10, and IL-10 were predictors of MOD; decreased IL-17 and MIP-1α separated CM-MOD from MOD; and increased IL-12p40 differentiated CM from CM-MOD. Data also suggest that the IL-17 pathway may contribute to malaria pathogenesis via different regulatory mechanisms and may represent an interesting target to mitigate the pathological processes in malaria-associated ARF.
authors.affiliation: CIIL-Center for Infection and Immunity of Lille, Team 04: Basic and Clinical Immunology of Parasitic Diseases, INSERM U1019, CNRS UMR 8204, Univ Lille Nord de France, Institut Pasteur de Lille, 1, rue du Prof Calmette, 59019, Lille Cedex, France. fabien.herbert@pasteur-lille.fr.
authors.forename: Fabien
authors.initials: F
authors.lastname: Herbert
authors.affiliation: CEA, DSV/iMETI, Immunology of Viral Infections and Autoimmune Diseases Research Unit, UMR1184, IDMIT Infrastructure, Fontenay-aux-Roses, France. nicolas.tchitchek@cea.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tchitchek
authors.affiliation: CIIL-Center for Infection and Immunity of Lille, Team 04: Basic and Clinical Immunology of Parasitic Diseases, INSERM U1019, CNRS UMR 8204, Univ Lille Nord de France, Institut Pasteur de Lille, 1, rue du Prof Calmette, 59019, Lille Cedex, France. dbansal2006@gmail.com.
authors.forename: Devendra
authors.initials: D
authors.lastname: Bansal
authors.affiliation: LPP, Laboratoire Paul Painlevé, INRIA Lille, Nord Europe, MODAL, Villeneuve-d'Ascq, France. julien.jacques@univ-lyon2.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Jacques
authors.affiliation: Department Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India. pathaksue@gmail.com.
authors.forename: Sulabha
authors.initials: S
authors.lastname: Pathak
authors.affiliation: Unité des Interactions Bactéries-Cellules, Institut Pasteur, 75015, Paris, France. christophe.becavin@pasteur.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Bécavin
authors.affiliation: Instituto Gulbenkian de Ciencia, Oeiras, Portugal. cfesel@igc.gulbenkian.pt.
authors.forename: Constantin
authors.initials: C
authors.lastname: Fesel
authors.affiliation: CIIL-Center for Infection and Immunity of Lille, Team 04: Basic and Clinical Immunology of Parasitic Diseases, INSERM U1019, CNRS UMR 8204, Univ Lille Nord de France, Institut Pasteur de Lille, 1, rue du Prof Calmette, 59019, Lille Cedex, France. esther.dalko@gmail.com.
authors.forename: Esther
authors.initials: E
authors.lastname: Dalko
authors.affiliation: CIIL-Center for Infection and Immunity of Lille, Team 04: Basic and Clinical Immunology of Parasitic Diseases, INSERM U1019, CNRS UMR 8204, Univ Lille Nord de France, Institut Pasteur de Lille, 1, rue du Prof Calmette, 59019, Lille Cedex, France. cazenave@pasteur.fr.|Immunologie, Immunopathologie, Immunothérapie, UPMC/CNRS UMR 7211, Paris, France. cazenave@pasteur.fr.
authors.forename: Pierre-André
authors.initials: PA
authors.lastname: Cazenave
authors.affiliation: LPP, Laboratoire Paul Painlevé, INRIA Lille, Nord Europe, MODAL, Villeneuve-d'Ascq, France. Cristian.Preda@polytech-lille.fr.
authors.forename: Cristian
authors.initials: C
authors.lastname: Preda
authors.affiliation: Institute of Life Sciences, Bhubaneswar, Odisha, India. ravindran8@gmail.com.
authors.forename: Balachandran
authors.initials: B
authors.lastname: Ravindran
authors.affiliation: Instituto Gulbenkian de Ciencia, Oeiras, Portugal. sharma@mailhost.tifr.res.in.
authors.forename: Shobhona
authors.initials: S
authors.lastname: Sharma
authors.affiliation: SCB Medical College, Cuttack, Odisha, India. bidyutdas@hotmail.com.
authors.forename: Bidyut
authors.initials: B
authors.lastname: Das
authors.affiliation: CIIL-Center for Infection and Immunity of Lille, Team 04: Basic and Clinical Immunology of Parasitic Diseases, INSERM U1019, CNRS UMR 8204, Univ Lille Nord de France, Institut Pasteur de Lille, 1, rue du Prof Calmette, 59019, Lille Cedex, France. sylviane.pied@pasteur-lille.fr.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Pied
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000503:physiopathology*; D054357:Chemokine CXCL10 / Q000097:blood / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000502:physiology*; D020381:Interleukin-17 / Q000097:blood / Q000502:physiology*; D016778:Malaria, Falciparum / Q000473:pathology / Q000503:physiopathology*; D009102:Multiple Organ Failure / Q000473:pathology / Q000503:physiopathology*
chemical_list: D054357:Chemokine CXCL10; D020381:Interleukin-17; D016753:Interleukin-10