IL-15 enhances the capacity of primary human macrophages to control Leishmania braziliensis infection by IL-32/vitamin D dependent and independent pathways.

Abstract

How human macrophages can control the intracellular infection with Leishmania is not completely understood. IL-15 and IL-32 are cytokines produced by monocytes/macrophages that can induce antimicrobial mechanisms. Here, we evaluated the effects of recombinant human IL-15 (rhIL-15) on primary human macrophage infection and response to L. braziliensis. Priming with rhIL-15 reduced the phagocytosis of L. braziliensis and increased the killing of the parasites in monocyte-derived macrophages from healthy donors. rhIL-15 induced TNFα and IL-32 in uninfected cells. After infection, the high levels of rhIL-15-induced TNFα and IL-32 were maintained. In addition, there was an increase of NO and an inhibition of the parasite-induced IL-10 production. Inhibition of NO reversed the leishmanicidal effects of rhIL-15. Although rhIL-15 did not increase L. braziliensis-induced reactive oxygen intermediates (ROS) production, inhibition of ROS reversed the control of infection induced by rhIL-15. Treatment of the cells with rhIL-32γ increased microbicidal capacity of macrophages in the presence of high levels of vitamin D (25D3), but not in low concentrations of this vitamin. rhIL-15 together with rhIL-32 lead to the highest control of the L. braziliensis infection in high concentrations of vitamin D. In this condition, NO and ROS mediated rhIL-32γ effects on microbicidal activity. The data showed that priming of human macrophages with rhIL-15 or rhIL-32γ results in the control of L. braziliensis infection through induction of NO and ROS. In addition, rhIL-32γ appears to synergize with rhIL-15 for the control of L. braziliensis infection in a vitamin D-dependent manner.

• Authors: Lucas Luiz de Lima Silva, Rodrigo Saar Gomes, Muriel Vilela Teodoro Silva, Leo A B Joosten, Fátima Ribeiro-Dias
• Journal: Parasitology international (Parasitol Int) Vol. 76 Pg. 102097 (Jun 2020) ISSN: 1873-0329 [Electronic] Netherlands
• PMID: 32114085 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Antiparasitic Agents
• IL15 protein, human
• IL32 protein, human
• Interleukin-15
• Interleukins
• Recombinant Proteins
• Vitamin D

Topics

• Antiparasitic Agents (metabolism, pharmacology)
• Interleukin-15 (metabolism, pharmacology)
• Interleukins (metabolism, pharmacology)
• Leishmania braziliensis (drug effects, physiology)
• Leishmaniasis, Cutaneous (drug therapy)
• Recombinant Proteins (metabolism)
• Signal Transduction
• Vitamin D (metabolism, pharmacology)