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

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 3

Resistance to KA is associated with enhanced IL-17 and IL-22 responses.

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Resistance to KA is associated with enhanced IL-17 and IL-22 responses. ...
(A) IL-17, IL-22, and Th1 and Th2 cytokine production by PBMCs from gp1, gp2, and gp3 subjects. Cytokines were quantified by ELISA in supernatants of PBMCs stimulated with 10 μg/ml of L. donovani extracts, as indicated in the Methods. IL-4 was undetectable or present in small amounts in all cultures. The data presented are the arithmetic means ± SEM. Cytokine scales (y axes) were set to allow for a 5-fold increase in the mean levels above those of the group with the lowest levels to be represented. (B) Resistance to KA was associated with high levels of both IL-22 and IL-17, whereas KA was associated with low levels of these cytokines. IL-17 and IL-22 levels were each assigned to 3 classes of equal size. The 3 classes for IL-17 were ≤15, 16–120, and 121–1,250 pg/ml. The 3 classes for IL-22 were <190, 190–890, and 900-40,000 pg/ml. Dark bars represent subjects with the lowest IL-17 and IL-22 levels. Data analysis is presented in Table 3.