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

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

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 4

IL-23, IL-6, and IL-1β production in cultures of PBMCs from subjects from the 3 clinical groups.

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IL-23, IL-6, and IL-1β production in cultures of PBMCs from subjects fro...
(A) IL-6 and IL-1β levels were higher in cultures of PBMCs from gp1 subjects than in those of cells from gp2 subjects, whereas no difference was observed for IL-23. Cultures were stimulated as described in Figure 2A. (B) PBMCs from KA subjects produced small amounts of IL-17 and IL-22, even in the presence of normal to high levels of the regulatory cytokines IL-6, IL-1β, and IL-23. IL-23, IL-6, and IL-1β levels in cultures (from gp1 and gp2) were assigned to 3 classes of equal size, and IL-17 and IL-22 levels are presented for each cytokine class. A nonparametric Kruskal-Wallis test showed a significant increase of IL-17 (P < 0.03) in increasing IL-23, IL-6, and IL-1β classes in cultures of PBMCs from resistant subjects. No significant increase of IL-17 was observed with increasing concentrations of IL-6 and IL-1β in cultures of PBMCs from gp2 subjects, whereas IL-17 did increase (P < 0.001) with increasing IL-23 concentrations in the same cultures. IL-22 increased (P < 0.05) with increasing IL-23, IL-6, and IL-1β concentrations in cultures of PBMCs from gp1 and gp2 subjects. The data presented are the arithmetic means ± SEM.