Indoleamine 2,3-dioxygenase-expressing dendritic cells form suppurative granulomas following Listeria monocytogenes infection

Abstract

Control of pathogens by formation of abscesses and granulomas is a major strategy of the innate immune system, especially when effector mechanisms of adaptive immunity are insufficient. We show in human listeriosis that DCs expressing indoleamine 2,3-dioxygenase (IDO), together with macrophages, are major cellular components of suppurative granulomas in vivo. Induction of IDO by DCs is a cell-autonomous response to Listeria monocytogenes infection and was also observed in other granulomatous infections with intracellular bacteria, such as Bartonella henselae. Reporting on our use of the clinically applied anti-TNF-α antibody infliximab, we further demonstrate in vitro that IDO induction is TNF-α dependent. Repression of IDO therefore might result in exacerbation of granulomatous diseases observed during anti-TNF-α therapy. These findings place IDO+ DCs not only at the intersection of innate and adaptive immunity but also at the forefront of bacterial containment in granulomatous infections.