A Virus Hosted in Malaria-Infected Blood Protects against T Cell-Mediated Inflammatory Diseases by Impairing DC Function in a Type I IFN-Dependent Manner
ABSTRACT Coinfections shape immunity and influence the development of inflammatory diseases, resulting in detrimental or beneficial outcome. Coinfections with concurrent Plasmodium species can alter malaria clinical evolution, and malaria infection itself can modulate autoimmune reactions. Yet, the...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2020-04-01
|
| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.03394-19 |
| _version_ | 1818838295039180800 |
|---|---|
| author | Ali Hassan Myriam F. Wlodarczyk Mehdi Benamar Emilie Bassot Anna Salvioni Sahar Kassem Antoine Berry Abdelhadi Saoudi Nicolas Blanchard |
| author_facet | Ali Hassan Myriam F. Wlodarczyk Mehdi Benamar Emilie Bassot Anna Salvioni Sahar Kassem Antoine Berry Abdelhadi Saoudi Nicolas Blanchard |
| author_sort | Ali Hassan |
| collection | DOAJ |
| description | ABSTRACT Coinfections shape immunity and influence the development of inflammatory diseases, resulting in detrimental or beneficial outcome. Coinfections with concurrent Plasmodium species can alter malaria clinical evolution, and malaria infection itself can modulate autoimmune reactions. Yet, the underlying mechanisms remain ill defined. Here, we demonstrate that the protective effects of some rodent malaria strains on T cell-mediated inflammatory pathologies are due to an RNA virus cohosted in malaria-parasitized blood. We show that live and extracts of blood parasitized by Plasmodium berghei K173 or Plasmodium yoelii 17X YM, protect against P. berghei ANKA-induced experimental cerebral malaria (ECM) and myelin oligodendrocyte glycoprotein (MOG)/complete Freund’s adjuvant (CFA)-induced experimental autoimmune encephalomyelitis (EAE), and that protection is associated with a strong type I interferon (IFN-I) signature. We detected the presence of the RNA virus lactate dehydrogenase-elevating virus (LDV) in the protective Plasmodium stabilates and we established that LDV infection alone was necessary and sufficient to recapitulate the protective effects on ECM and EAE. In ECM, protection resulted from an IFN-I-mediated reduction in the abundance of splenic conventional dendritic cell and impairment of their ability to produce interleukin (IL)-12p70, leading to a decrease in pathogenic CD4+ Th1 responses. In EAE, LDV infection induced IFN-I-mediated abrogation of IL-23, thereby preventing the differentiation of granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing encephalitogenic CD4+ T cells. Our work identifies a virus cohosted in several Plasmodium stabilates across the community and deciphers its major consequences on the host immune system. More generally, our data emphasize the importance of considering contemporaneous infections for the understanding of malaria-associated and autoimmune diseases. IMPORTANCE Any infection modifies the host immune status, potentially ameliorating or aggravating the pathophysiology of a simultaneous inflammatory condition. In the course of investigating how malaria infection modulates the severity of contemporaneous inflammatory diseases, we identified a nonpathogenic mouse virus in stabilates of two widely used rodent parasite lines: Plasmodium berghei K173 and Plasmodium yoelii 17X YM. We established that the protective effects of these Plasmodium lines on cerebral malaria and multiple sclerosis are exclusively due to this virus. The virus induces a massive type I interferon (IFN-I) response and causes quantitative and qualitative defects in the ability of dendritic cells to promote pathogenic T cell responses. Beyond revealing a possible confounding factor in rodent malaria models, our work uncovers some bases by which a seemingly innocuous viral (co)infection profoundly changes the immunopathophysiology of inflammatory diseases. |
| first_indexed | 2024-12-19T03:36:07Z |
| format | Article |
| id | doaj.art-3a22cb4a960e438f82336675f40a6899 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T03:36:07Z |
| publishDate | 2020-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-3a22cb4a960e438f82336675f40a68992022-12-21T20:37:22ZengAmerican Society for MicrobiologymBio2150-75112020-04-0111210.1128/mBio.03394-19A Virus Hosted in Malaria-Infected Blood Protects against T Cell-Mediated Inflammatory Diseases by Impairing DC Function in a Type I IFN-Dependent MannerAli Hassan0Myriam F. Wlodarczyk1Mehdi Benamar2Emilie Bassot3Anna Salvioni4Sahar Kassem5Antoine Berry6Abdelhadi Saoudi7Nicolas Blanchard8Centre de Physiopathologie Toulouse-Purpan (CPTP), Université de Toulouse, Toulouse, FranceCentre de Physiopathologie Toulouse-Purpan (CPTP), Université de Toulouse, Toulouse, FranceCentre de Physiopathologie Toulouse-Purpan (CPTP), Université de Toulouse, Toulouse, FranceCentre de Physiopathologie Toulouse-Purpan (CPTP), Université de Toulouse, Toulouse, FranceCentre de Physiopathologie Toulouse-Purpan (CPTP), Université de Toulouse, Toulouse, FranceCentre de Physiopathologie Toulouse-Purpan (CPTP), Université de Toulouse, Toulouse, FranceCentre de Physiopathologie Toulouse-Purpan (CPTP), Université de Toulouse, Toulouse, FranceCentre de Physiopathologie Toulouse-Purpan (CPTP), Université de Toulouse, Toulouse, FranceCentre de Physiopathologie Toulouse-Purpan (CPTP), Université de Toulouse, Toulouse, FranceABSTRACT Coinfections shape immunity and influence the development of inflammatory diseases, resulting in detrimental or beneficial outcome. Coinfections with concurrent Plasmodium species can alter malaria clinical evolution, and malaria infection itself can modulate autoimmune reactions. Yet, the underlying mechanisms remain ill defined. Here, we demonstrate that the protective effects of some rodent malaria strains on T cell-mediated inflammatory pathologies are due to an RNA virus cohosted in malaria-parasitized blood. We show that live and extracts of blood parasitized by Plasmodium berghei K173 or Plasmodium yoelii 17X YM, protect against P. berghei ANKA-induced experimental cerebral malaria (ECM) and myelin oligodendrocyte glycoprotein (MOG)/complete Freund’s adjuvant (CFA)-induced experimental autoimmune encephalomyelitis (EAE), and that protection is associated with a strong type I interferon (IFN-I) signature. We detected the presence of the RNA virus lactate dehydrogenase-elevating virus (LDV) in the protective Plasmodium stabilates and we established that LDV infection alone was necessary and sufficient to recapitulate the protective effects on ECM and EAE. In ECM, protection resulted from an IFN-I-mediated reduction in the abundance of splenic conventional dendritic cell and impairment of their ability to produce interleukin (IL)-12p70, leading to a decrease in pathogenic CD4+ Th1 responses. In EAE, LDV infection induced IFN-I-mediated abrogation of IL-23, thereby preventing the differentiation of granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing encephalitogenic CD4+ T cells. Our work identifies a virus cohosted in several Plasmodium stabilates across the community and deciphers its major consequences on the host immune system. More generally, our data emphasize the importance of considering contemporaneous infections for the understanding of malaria-associated and autoimmune diseases. IMPORTANCE Any infection modifies the host immune status, potentially ameliorating or aggravating the pathophysiology of a simultaneous inflammatory condition. In the course of investigating how malaria infection modulates the severity of contemporaneous inflammatory diseases, we identified a nonpathogenic mouse virus in stabilates of two widely used rodent parasite lines: Plasmodium berghei K173 and Plasmodium yoelii 17X YM. We established that the protective effects of these Plasmodium lines on cerebral malaria and multiple sclerosis are exclusively due to this virus. The virus induces a massive type I interferon (IFN-I) response and causes quantitative and qualitative defects in the ability of dendritic cells to promote pathogenic T cell responses. Beyond revealing a possible confounding factor in rodent malaria models, our work uncovers some bases by which a seemingly innocuous viral (co)infection profoundly changes the immunopathophysiology of inflammatory diseases.https://journals.asm.org/doi/10.1128/mBio.03394-19CD4 T cellRNA virusautoimmunitycoinfectiondendritic cellsinflammation |
| spellingShingle | Ali Hassan Myriam F. Wlodarczyk Mehdi Benamar Emilie Bassot Anna Salvioni Sahar Kassem Antoine Berry Abdelhadi Saoudi Nicolas Blanchard A Virus Hosted in Malaria-Infected Blood Protects against T Cell-Mediated Inflammatory Diseases by Impairing DC Function in a Type I IFN-Dependent Manner mBio CD4 T cell RNA virus autoimmunity coinfection dendritic cells inflammation |
| title | A Virus Hosted in Malaria-Infected Blood Protects against T Cell-Mediated Inflammatory Diseases by Impairing DC Function in a Type I IFN-Dependent Manner |
| title_full | A Virus Hosted in Malaria-Infected Blood Protects against T Cell-Mediated Inflammatory Diseases by Impairing DC Function in a Type I IFN-Dependent Manner |
| title_fullStr | A Virus Hosted in Malaria-Infected Blood Protects against T Cell-Mediated Inflammatory Diseases by Impairing DC Function in a Type I IFN-Dependent Manner |
| title_full_unstemmed | A Virus Hosted in Malaria-Infected Blood Protects against T Cell-Mediated Inflammatory Diseases by Impairing DC Function in a Type I IFN-Dependent Manner |
| title_short | A Virus Hosted in Malaria-Infected Blood Protects against T Cell-Mediated Inflammatory Diseases by Impairing DC Function in a Type I IFN-Dependent Manner |
| title_sort | virus hosted in malaria infected blood protects against t cell mediated inflammatory diseases by impairing dc function in a type i ifn dependent manner |
| topic | CD4 T cell RNA virus autoimmunity coinfection dendritic cells inflammation |
| url | https://journals.asm.org/doi/10.1128/mBio.03394-19 |
| work_keys_str_mv | AT alihassan avirushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT myriamfwlodarczyk avirushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT mehdibenamar avirushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT emiliebassot avirushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT annasalvioni avirushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT saharkassem avirushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT antoineberry avirushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT abdelhadisaoudi avirushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT nicolasblanchard avirushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT alihassan virushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT myriamfwlodarczyk virushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT mehdibenamar virushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT emiliebassot virushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT annasalvioni virushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT saharkassem virushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT antoineberry virushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT abdelhadisaoudi virushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner AT nicolasblanchard virushostedinmalariainfectedbloodprotectsagainsttcellmediatedinflammatorydiseasesbyimpairingdcfunctioninatypeiifndependentmanner |