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IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani
Maira G.R. Pitta, … , Sayda Hassan El-Safi, Alain Dessein
Maira G.R. Pitta, … , Sayda Hassan El-Safi, Alain Dessein
Published July 13, 2009
Citation Information: J Clin Invest. 2009;119(8):2379-2387. https://doi.org/10.1172/JCI38813.
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Research Article Infectious disease Article has an altmetric score of 3

IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani

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Abstract

IL-17 and IL-22 have been shown to increase protection against certain bacteria and fungal pathogens in experimental models. However, no human studies have demonstrated a crucial role of IL-17 and IL-22 in protection against infections. We show here that Leishmania donovani, which can cause the lethal visceral disease Kala Azar (KA), stimulates the differentiation of Th17 cells, which produce IL-17, IL-22, and IFN-γ. Analysis of Th1, Th2, and Th17 cytokine responses by cultured PBMCs from individuals in a cohort of subjects who developed KA or were protected against KA during a severe outbreak showed that IL-17 and IL-22 were strongly and independently associated with protection against KA. Our results suggest that, along with Th1 cytokines, IL-17 and IL-22 play complementary roles in human protection against KA, and that a defect in Th17 induction may increase the risk of KA.

Authors

Maira G.R. Pitta, Audrey Romano, Sandrine Cabantous, Sandrine Henri, Awad Hammad, Bouréma Kouriba, Laurent Argiro, Musa el Kheir, Bruno Bucheton, Charles Mary, Sayda Hassan El-Safi, Alain Dessein

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Figure 1

Induction of IL-17 and IL-22 by L. donovani in cultures of PBMCs from healthy subjects.

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Induction of IL-17 and IL-22 by L. donovani in cultures of PBMCs from he...
(A) The production of IL-17 and IL-22 in cultures of PBMCs from healthy donors required priming with whole L. donovani parasites. Boosting was achieved using parasites or parasite extracts. Priming (on day 0; stimulation 1) and boost (on day 7; stimulation 2) were performed with opsonized (OpsLd) or non-opsonized (Ld) heat-killed L. donovani parasites or parasite extracts (Ld-ext). IL-17 and IL-22 were quantified by ELISA on days 7, 11, and 15. Two representative experiments (Exp 1 and Exp 2) from a series of 10 are shown. (B) IL-17 and IL-22 were produced by CD4+ T cells. CD4+ T cells were purified from the 12-day cultures of PBMCs primed and boosted with OpsLd. Purified CD4+ T cells were then stimulated for 48 hours with PMA plus ionomycin, concanavalin A (ConA), or phytohemagglutinin (PHA). IL-17 and IL-22 were quantified by ELISA. Three independent experiments with cells from different donors are shown. (C) Phenotypic characterization of IL-17+CD4+ T cells in cultures of normal PBMCs stimulated with OpsLd. Normal PBMCs were primed and boosted with OpsLd. Five days after the second stimulation, cells were stimulated with PMA plus ionomycin plus monensin for 5 hours. The x axis represents the fluorescence intensity after either CD4 labeling or IFN-γ labeling. The y axis corresponds to IL-17 labeling. Horizontal and vertical bars define the upper fluorescence intensity observed with labeled control cells. The numbers in each quadrant represent the percentage of cells in that quadrant relative to the total number of cells included in the analysis.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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