Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis
| العنوان: | Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis |
|---|---|
| المؤلفون: | Daniel T. Utzschneider, Mary-Anne Hartley, Matteo Rossi, Stephen M. Beverley, Remzi Onur Eren, Catherine Ronet, Florence Prevel, Maria Grazia Cusi, Patrik Castiglioni, Nicolas Fasel, F. Matthew Kuhlmann, Dietmar Zehn, Chantal Desponds |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 19, pp. 4987-4992 Proceedings of the National Academy of Sciences |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Leishmaniasis, Mucocutaneous, 0301 basic medicine, Animals, Coinfection, Interferon Type I/genetics, Interferon Type I/immunology, Leishmania guyanensis/immunology, Leishmania guyanensis/virology, Leishmaniasis, Mucocutaneous/genetics, Leishmaniasis, Mucocutaneous/immunology, Leishmaniasis, Mucocutaneous/pathology, Leishmaniavirus/immunology, Lymphocytic Choriomeningitis/genetics, Lymphocytic Choriomeningitis/immunology, Lymphocytic Choriomeningitis/pathology, Lymphocytic choriomeningitis virus/immunology, Mice, Mice, Knockout, Phlebotomus Fever/genetics, Phlebotomus Fever/immunology, Phlebotomus Fever/pathology, Sandfly fever Naples virus/immunology, Leishmania RNA virus 1, Leishmania subgenus Viannia, Totiviridae, arboviruses, trypanosomatid protozoan parasite, viruses, Leishmaniavirus, 030231 tropical medicine, Leishmania guyanensis, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis, Virus, 03 medical and health sciences, 0302 clinical medicine, parasitic diseases, medicine, Lymphocytic choriomeningitis virus, Multidisciplinary, biology, Sandfly fever Naples virus, Biological Sciences, medicine.disease, Leishmania, biology.organism_classification, Acquired immune system, Virology, 3. Good health, Phlebotomus Fever, 030104 developmental biology, Interferon Type I, Immunology, Interferon type I, medicine.drug |
| الوصف: | The presence of the endogenous Leishmania RNA virus 1 (LRV1) replicating stably within some parasite species has been associated with the development of more severe forms of leishmaniasis and relapses after drug treatment in humans. Here, we show that the disease-exacerbatory role of LRV1 relies on type I IFN (type I IFNs) production by macrophages and signaling in vivo. Moreover, infecting mice with the LRV1-cured Leishmania guyanensis ( LgyLRV1 - ) strain of parasites followed by type I IFN treatment increased lesion size and parasite burden, quantitatively reproducing the LRV1-bearing ( LgyLRV1 + ) infection phenotype. This finding suggested the possibility that exogenous viral infections could likewise increase pathogenicity, which was tested by coinfecting mice with L. guyanensis and lymphocytic choriomeningitis virus (LCMV), or the sand fly-transmitted arbovirus Toscana virus (TOSV). The type I IFN antiviral response increased the pathology of L. guyanensis infection, accompanied by down-regulation of the IFN-γ receptor normally required for antileishmanial control. Further, LCMV coinfection of IFN-γ-deficient mice promoted parasite dissemination to secondary sites, reproducing the LgyLRV1 + metastatic phenotype. Remarkably, LCMV coinfection of mice that had healed from L. guyanensis infection induced reactivation of disease pathology, overriding the protective adaptive immune response. Our findings establish that type I IFN-dependent responses, arising from endogenous viral elements (dsRNA/LRV1), or exogenous coinfection with IFN-inducing viruses, are able to synergize with New World Leishmania parasites in both primary and relapse infections. Thus, viral infections likely represent a significant risk factor along with parasite and host factors, thereby contributing to the pathological spectrum of human leishmaniasis. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5c51b8002599b4fccbc5c3e303031b45 http://hdl.handle.net/11365/1006794 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5c51b8002599b4fccbc5c3e303031b45 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |