Eimeria falciformis infection of the mouse caecum identifies opposing roles of IFNγ-regulated host pathways for the parasite development
| Autor: | Nishith Gupta, Richard Lucius, Manuela Schmid, Emanuel Heitlinger, Hans-Joachim Mollenkopf, Simone Spork |
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| Rok vydání: | 2013 |
| Předmět: |
Chemokine
Receptors CXCR3 Immunology Inflammation Biology CXCR3 Models Biological Host-Parasite Interactions Interferon-gamma Mice Immune system medicine Immunology and Allergy Animals Cluster Analysis Indoleamine-Pyrrole 2 3 -Dioxygenase Cecum Monomeric GTP-Binding Proteins Receptors Interferon Mice Knockout Coccidiosis Intracellular parasite Gene Expression Profiling Tryptophan Acquired immune system Intestinal epithelium Cell biology Disease Models Animal Gene Expression Regulation biology.protein Eimeria medicine.symptom Signal transduction Signal Transduction |
| Zdroj: | Mucosal immunology. 7(4) |
| ISSN: | 1935-3456 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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