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.

Fabien Herbert (1) , Nicolas Tchitchek (2) , Devendra Bansal (1) , Julien Jacques (3) , Sulabha Pathak (4) , Christophe Becavin (5) , Constantin Fesel (6) , Esther Dalko (1) , Pierre-André Cazenave (1, 7) , Cristian Preda (3) , Balachandran Ravindran (8) , Shobhona Sharma (6) , Bidyut Das (9) , Sylviane Pied (1)

1 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
2 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes
3 LPP - Laboratoire Paul Painlevé - UMR 8524
4 TIFR - Tata Institute for Fundamental Research
5 UIBC - Interactions Bactéries-Cellules
6 IGC - Instituto Gulbenkian de Ciência [Oeiras]
7 I3 - Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière]
8 Indian Institute of technology Bhubaneswar
9 SCB Medical College - Sriram Chandra Bhanj Medical College [Cuttack]

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. CONCLUSION: 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.

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

Domaines: Maladies infectieuses; Urologie et Néphrologie

Fabien Herbert, Nicolas Tchitchek, Devendra Bansal, Julien Jacques, Sulabha Pathak, et al.. 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, 2015, 13, pp.369. ⟨10.1186/s12967-015-0731-6⟩. ⟨hal-02051283⟩