title: Lessons from other diseases: granulomatous inflammation in leishmaniasis.
abstract: The Leishmania granuloma shares some, though not all, properties with that formed following mycobacterial infection. As a simplified, noncaseating granuloma composed of relatively few and largely mononuclear cell populations, it provides a tractable model system to investigate intra-granuloma cellular dynamics, immune regulation, and antimicrobial resistance. Here, the occurrence of granulomatous pathology across the spectrum of leishmaniasis, in humans and animal reservoir hosts, is first described. However, this review focuses on the process of hepatic granuloma formation as studied in rodent models of visceral leishmaniasis, starting from the initial infection of Kupffer cells to the involution of the granuloma after pathogen clearance. It describes how the application of intravital imaging and the use of computational modeling have changed some of our thoughts on granuloma function, and illustrates how host-directed therapies have been used to manipulate granuloma form and function for therapeutic benefit. Where appropriate, lessons that may be equally applicable across the spectrum of granulomatous diseases are highlighted.
authors.affiliation: Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, Heslington, York, YO10 5DD, UK. paul.kaye@york.ac.uk.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kaye
authors.affiliation: QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Queensland, Australia, 4006.
authors.forename: Lynette
authors.initials: L
authors.lastname: Beattie
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006099:Granuloma / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007107:Immune System / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D007891:Leishmania / Q000502:physiology*; D007896:Leishmaniasis / Q000150:complications / Q000276:immunology* / Q000469:parasitology*; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D051379:Mice; D012157:Mononuclear Phagocyte System / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology
chemical_list: D000981:Antiprotozoal Agents; D018925:Chemokines; D016207:Cytokines
keywords: Computational models; Granuloma; Intravital imaging; Leishmania; Mouse models