Histoplasma capsulatum preferentially induces IDO in the lung. (April 2013)

• Record Type: Journal Article
• Authors: Hage, Chadi A.; Horan, Daniel J.; Durkin, Michelle; Connolly, Patricia; Desta, Zeruesenay; Skaar, Todd C.; Knox, Kenneth S.; Wheat, L. Joseph
• Is Part Of: Medical mycology. Volume 51:Number 3(2013)
• Page Start: 270
• Page End: 279
• Publication Date: 2013-04
• Subjects: Medical mycology -- Periodicals; Veterinary mycology -- Periodicals; Mycology -- Periodicals; Mycoses -- Periodicals; Pathogenic fungi -- Periodicals; 616.969005
• DOI: 10.3109/13693786.2012.710857
• Languages: English
• ISSNs: 1369-3786

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>Histoplasma capsulatum</italic>. 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 <italic>in vivo. Histoplasma</italic> 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, <italic>P</italic> < 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 <italic>Histoplasma</italic>-induced granulomas. IDO inhibition prior to infection reduced fungal burdens and inflammation in lungs and spleen. <italic>Histoplasma</italic> preferentially induces lung IDO, as early as one week after infection. IDO appears to modulate the immune response to <italic>Histoplasma</italic> infection.</p> </abstract>