title: IL-17A promotes macrophage effector mechanisms against Trypanosoma cruzi by trapping parasites in the endolysosomal compartment.
abstract: The contribution of the IL-23-IL-17A pathway to resistance against extracellular bacterial infections is well established, whereas its role in immunity to intracellular pathogens is much less clear. To analyze the contribution of the IL-23-IL-17A-axis to resistance against Trypanosoma cruzi infection, we infected IL-23p19(-/-) mice and IL-17A(-/-) mice with T. cruzi. Both mouse strains were susceptible to T. cruzi infection despite strong Th1 immune responses. In vitro experiments revealed that IL-17A, but not IL-23, directly stimulates macrophages to internalize T. cruzi parasites by phagocytosis, which is in contrast to the active invasion process normally used by T. cruzi. In contrast to the active entry of parasites into macrophages, the IL-17A-driven phagocytosis prolonged residency of parasites in the endosomal/lysosomal compartment of the macrophage, which subsequently led to eradication of parasites. This IL-17A-dependent mechanism represents a novel function of IL-17A trapping pathogens in endosomal/lysosomal compartments and enhancing exposure time to antimicrobial effectors of the macrophage.
authors.affiliation: Infection Immunology, Research Center Borstel, 23845 Borstel, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Erdmann
authors.forename: Caroline
authors.initials: C
authors.lastname: Roßnagel
authors.forename: Julia
authors.initials: J
authors.lastname: Böhme
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Thomas
authors.initials: T
authors.lastname: Jacobs
authors.forename: Ulrich E
authors.initials: UE
authors.lastname: Schaible
authors.forename: Christoph
authors.initials: C
authors.lastname: Hölscher
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D011992:Endosomes / Q000276:immunology* / Q000469:parasitology; D005260:Female; D006790:Host-Parasite Interactions / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053760:Interleukin-23 Subunit p19 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008247:Lysosomes / Q000276:immunology* / Q000469:parasitology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D018512:Parasitemia / Q000235:genetics / Q000276:immunology / Q000401:mortality; D010587:Phagocytosis / Q000276:immunology; D015996:Survival Rate; D014349:Trypanosoma cruzi / Q000235:genetics / Q000276:immunology* / Q000502:physiology
chemical_list: D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19