Histoplasma capsulatum preferentially induces IDO in the lung

Chadi A. Hage, Daniel J. Horan, Michelle Durkin, Patricia Connolly, Zeruesenay Desta, Todd C. Skaar, Kenneth S. Knox, L. Joseph Wheat

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Indoleamine 2,3 dioxygenase (IDO) plays an important role in immunoregulation as it is involved in downregulating immune responses to infections. We sought to characterize IDO activity in histoplasmosis and to do so, C57Bl6 mice were infected intranasally with Histoplasma capsulatum. After infection, lung and spleen IDO activity was assessed by HPLC and IDO expression by qRT-PCR. The distribution of IDO was determined by immunohistochemical staining. Cytokine levels were measured in lung and spleen homogenates using cytokine bead array. Fungal burden was quantified by culture. Subcutaneous pellets containing methyltryptophane (1-MT) were employed to inhibit IDO in vivo. Histoplasma infection strongly induced functional lung IDO, with activity at its highest at weeks 1 and 2 and then decreased thereafter as the mice cleared the infection. Lung IDO activity positively correlated with the fungal burden (Rho = 0.845), interferon-γ (Rho = 0.839) and tumor necrosis factor-α (Rho = 0.791) levels, P < 0.001. In contrast, spleen IDO activity was not induced despite high infection burden and cytokine levels. IDO expressing cells were predominately located at the ring edge of Histoplasma-induced granulomas. IDO inhibition prior to infection reduced fungal burdens and inflammation in lungs and spleen. Histoplasma preferentially induces lung IDO, as early as one week after infection. IDO appears to modulate the immune response to Histoplasma infection.

Original languageEnglish (US)
Pages (from-to)270-279
Number of pages10
JournalMedical mycology
Volume51
Issue number3
DOIs
StatePublished - Apr 2013

Keywords

  • 3 dioxygenase (IDO)
  • Cytokines
  • Histoplasmosis
  • Indoleamine 2
  • Kynurenine

ASJC Scopus subject areas

  • Infectious Diseases

Fingerprint Dive into the research topics of 'Histoplasma capsulatum preferentially induces IDO in the lung'. Together they form a unique fingerprint.

  • Cite this

    Hage, C. A., Horan, D. J., Durkin, M., Connolly, P., Desta, Z., Skaar, T. C., Knox, K. S., & Wheat, L. J. (2013). Histoplasma capsulatum preferentially induces IDO in the lung. Medical mycology, 51(3), 270-279. https://doi.org/10.3109/13693786.2012.710857