Innate Immune Basis for Rift Valley Fever Susceptibility in Mouse Models.
Rashida LathanDominique Simon-ChazottesGrégory JouvionOphélie GodonMarie MalissenMarie FlamandPierre BruhnsJean-Jacques PanthierPublished in: Scientific reports (2017)
Rift Valley fever virus (RVFV) leads to varied clinical manifestations in animals and in humans that range from moderate fever to fatal illness, suggesting that host immune responses are important determinants of the disease severity. We investigated the immune basis for the extreme susceptibility of MBT/Pas mice that die with mild to acute hepatitis by day 3 post-infection compared to more resistant BALB/cByJ mice that survive up to a week longer. Lower levels of neutrophils observed in the bone marrow and blood of infected MBT/Pas mice are unlikely to be causative of increased RVFV susceptibility as constitutive neutropenia in specific mutant mice did not change survival outcome. However, whereas MBT/Pas mice mounted an earlier inflammatory response accompanied by higher amounts of interferon (IFN)-α in the serum compared to BALB/cByJ mice, they failed to prevent high viral antigen load. Several immunological alterations were uncovered in infected MBT/Pas mice compared to BALB/cByJ mice, including low levels of leukocytes that expressed type I IFN receptor subunit 1 (IFNAR1) in the blood, spleen and liver, delayed leukocyte activation and decreased percentage of IFN-γ-producing leukocytes in the blood. These observations are consistent with the complex mode of inheritance of RVFV susceptibility in genetic studies.
Keyphrases
- high fat diet induced
- immune response
- bone marrow
- inflammatory response
- wild type
- dendritic cells
- randomized controlled trial
- mesenchymal stem cells
- sars cov
- adipose tissue
- intensive care unit
- metabolic syndrome
- toll like receptor
- extracorporeal membrane oxygenation
- peripheral blood
- hepatitis b virus
- acute respiratory distress syndrome
- atomic force microscopy
- binding protein
- double blind