title: Eimeria falciformis infection of the mouse caecum identifies opposing roles of IFNγ-regulated host pathways for the parasite development.
abstract: Intracellular parasites reprogram host functions for their survival and reproduction. The extent and relevance of parasite-mediated host responses in vivo remains poorly studied, however. We utilized Eimeria falciformis, a parasite infecting the mouse intestinal epithelium, to identify and validate host determinants of parasite infection. Most prominent mouse genes induced during the onset of asexual and sexual growth of parasite comprise interferon γ (IFNγ)-regulated factors, e.g., immunity-related GTPases (IRGA6/B6/D/M2/M3), guanylate-binding proteins (GBP2/3/5/6/8), chemokines (CxCL9-11), and several enzymes of the kynurenine pathway including indoleamine 2,3-dioxygenase 1 (IDO1). These results indicated a multifarious innate defense (tryptophan catabolism, IRG, GBP, and chemokine signaling), and a consequential adaptive immune response (chemokine-cytokine signaling and lymphocyte recruitment). The inflammation- and immunity-associated transcripts were increased during the course of infection, following influx of B cells, T cells, and macrophages to the parasitized caecum tissue. Consistently, parasite growth was enhanced in animals inhibited for CxCr3, a major receptor for CxCL9-11 present on immune cells. Interestingly, despite a prominent induction, mouse IRGB6 failed to bind and disrupt the parasitophorous vacuole, implying an immune evasion by E. falciformis. Furthermore, oocyst output was impaired in IFNγ-R(-/-) and IDO1(-/-) mice, both of which suggest a subversion of IFNγ signaling by the parasite to promote its growth.
authors.affiliation: Department of Molecular Parasitology, Humboldt University, Berlin, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Schmid
authors.affiliation: Department of Molecular Parasitology, Humboldt University, Berlin, Germany.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Heitlinger
authors.affiliation: Department of Molecular Parasitology, Humboldt University, Berlin, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Spork
authors.affiliation: Microarray and Genomics Core Facility, Max-Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Mollenkopf
authors.affiliation: Department of Molecular Parasitology, Humboldt University, Berlin, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Lucius
authors.affiliation: 1] Department of Molecular Parasitology, Humboldt University, Berlin, Germany [2] Department of Parasitology, Max-Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Nishith
authors.initials: N
authors.lastname: Gupta
mesh_terms: D000818:Animals; D002432:Cecum / Q000378:metabolism* / Q000469:parasitology*; D016000:Cluster Analysis; D003048:Coccidiosis / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology*; D004195:Disease Models, Animal; D004539:Eimeria; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006790:Host-Parasite Interactions; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics; D015398:Signal Transduction; D014364:Tryptophan / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D020559:Monomeric GTP-Binding Proteins; D054367:Receptors, CXCR3; D017471:Receptors, Interferon; D014364:Tryptophan; D000096743:Interferon gamma Receptor; C583637:IDO1 protein, mouse; C092499:Tgtp protein, mouse