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

Journal of Translational Medicine

Research

Nicolas Tchitchek¹  Esther Dalko²  Fabien Herbert²  Devendra Bansal²  Sylviane Pied²  Pierre-André Cazenave³  Sulabha Pathak⁴  Balachandran Ravindran⁵  Constantin Fesel⁶  Shobhona Sharma⁶  Julien Jacques⁷  Cristian Preda⁷  Bidyut Das⁸  Christophe Bécavin⁹ 

[1] CEA, DSV/iMETI, Immunology of Viral Infections and Autoimmune Diseases Research Unit, UMR1184, IDMIT Infrastructure, Fontenay-aux-Roses, France;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;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;Immunologie, Immunopathologie, Immunothérapie, UPMC/CNRS UMR 7211, Paris, France;Department Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India;Institute of Life Sciences, Bhubaneswar, Odisha, India;Instituto Gulbenkian de Ciencia, Oeiras, Portugal;LPP, Laboratoire Paul Painlevé, INRIA Lille, Nord Europe, MODAL, Villeneuve-d’Ascq, France;SCB Medical College, Cuttack, Odisha, India;Unité des Interactions Bactéries-Cellules, Institut Pasteur, 75015, Paris, France;

关键词: Plasmodium falciparum;    Severe malaria;    Cerebral malaria;    Acute-renal failure;    Malaria associated organ failure;    IL-17;    Cytokines;    Biomarkers;   

DOI  :  10.1186/s12967-015-0731-6

 received in 2015-04-10, accepted in 2015-09-09,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundPlasmodium 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.MethodsP. 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.ResultsOf 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.ConclusionWe 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.

【 授权许可】

CC BY   
© Herbert et al. 2015