Leishmania major attenuates host immunity by stimulating local indoleamine 2,3-dioxygenase expression

Levi H C Makala, Babak Baban, Henrique Lemos, Ahmed R. El-Awady, Phillip R. Chandler, De Yan Hou, David H. Munn, Andrew L. Mellor

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52 Scopus citations

Abstract

Inflammation stimulates immunity but can create immune privilege in some settings. Here, we show that cutaneous Leishmania major infection stimulated expression of the immune regulatory enzyme indoleamine 2,3 dioxygenase (IDO) in local lymph nodes. Induced IDO attenuated the T cell stimulatory functions of dendritic cells and suppressed local T cell responses to exogenous and nominal parasite antigens. IDO ablation reduced local inflammation and parasite burdens, as did pharmacologic inhibition of IDO in mice with established infections. IDO ablation also enhanced local expression of proinflammatory cytokines and induced some CD4+ T cells to express interleukin (IL) 17. These findings showed that IDO induced by L. major infection attenuated innate and adaptive immune responses. Thus, IDO acts as a molecular switch regulating host responses, and IDO inhibitor drugs are a potential new approach to enhance host immunity to established leishmania infections.

Original languageEnglish (US)
Pages (from-to)715-725
Number of pages11
JournalJournal of Infectious Diseases
Volume203
Issue number5
DOIs
Publication statusPublished - Mar 1 2011

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Makala, L. H. C., Baban, B., Lemos, H., El-Awady, A. R., Chandler, P. R., Hou, D. Y., ... Mellor, A. L. (2011). Leishmania major attenuates host immunity by stimulating local indoleamine 2,3-dioxygenase expression. Journal of Infectious Diseases, 203(5), 715-725. https://doi.org/10.1093/infdis/jiq095