Inducible Nitric Oxide Synthase is required for parasite restriction and inflammatory modulation during Neospora caninum infection
| Autor: | Lourenço Faria Costa, Vanessa dos Santos Miranda, Silas Silva Santana, Ana Cláudia Arantes Marques Pajuaba, Patrício da Silva Cardoso Barros, Eliézer Lucas Pires Ramos, Flávia Batista Ferreira, Caroline M. Mota, José Roberto Mineo, Tiago W. P. Mineo |
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| Rok vydání: | 2019 |
| Předmět: |
Nitric Oxide Synthase Type II
Inflammation Nitric Oxide Parasite load Microbiology Nitric oxide Proinflammatory cytokine Interferon-gamma Mice chemistry.chemical_compound Immune system Immunity parasitic diseases medicine Animals General Veterinary biology Coccidiosis Interleukin-12 Subunit p40 Macrophages Neospora General Medicine biology.organism_classification Neospora caninum Mice Inbred C57BL Nitric oxide synthase chemistry biology.protein Parasitology medicine.symptom |
| Zdroj: | Veterinary Parasitology. 276:108990 |
| ISSN: | 0304-4017 |
| Popis: | Neospora caninum infection is an important cause of neuromuscular disease in dogs and abortion in cattle, leading to significant economic losses in beef and dairy industries. The protective immunity against apicomplexan parasites, specifically Toxoplasma gondii and N. caninum, is typically achieved by inducing an IL-12-driven Th1 immune response. IL-12 stimulates IFN-γ production, which activates Inducible Nitric Oxide Synthase (iNOS) and promotes consequent Nitric Oxide (NO) synthesis, classically described as one of the main effector mechanisms for parasite elimination. Here, we aimed to evaluate the role played by iNOS during N. caninum infection. Our results show that N. caninum infection in C57BL/6 wild type (WT) mice induce NO production in vivo and in vitro. In agreement, iNOS deficient mice, as well as WT mice treated with iNOS inhibitor aminoguanidine, succumbed during acute infection with a dose lethal to 50 % of the WT mice, and presented significant increase in parasite load when submitted to sub-lethal infection protocols. Interestingly, the lack of control of parasite proliferation observed in iNOS-/- mice was associated with notable CNS inflammation and increased production of the main systemic proinflammatory cytokines (IL-12, IFN-γ, IL-6, TNF and IL-17A). Taken together, our findings show that iNOS plays an important role in restricting N. caninum replication, while also modulates the inflammatory process induced by the infection. |
| Databáze: | OpenAIRE |
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