Maternal Immunity and Vaccination Influence Disease Severity in Progeny in a Novel Mast Cell-Deficient Mouse Model of Severe Dengue.

Journal Article (Journal Article)

Sub-neutralizing concentrations of antibodies in dengue infected patients is a major risk factor for the development of dengue hemorrhagic fever and dengue shock syndrome. Here, we describe a mouse model with a deficiency in mast cells (MCs) in addition to a deficiency in Type-I and II IFN receptors for studying dengue virus (DENV) infection. We used this model to understand the influence of MCs in a maternal antibody-dependent model of severe dengue, where offspring born to DENV-immune mothers are challenged with a heterologous DENV serotype. Mice lacking both MCs and IFN receptors were found susceptible to primary DENV infection and showed morbidity and mortality. When these mice were immunized, pups born to DENV-immune mothers were found to be protected for a longer duration from a heterologous DENV challenge. In the absence of MCs and type-I interferon signaling, IFN-γ was found to protect pups born to naïve mothers but had the opposite effect on pups born to DENV-immune mothers. Our results highlight the complex interactions between MCs and IFN-signaling in influencing the role of maternal antibodies in DENV-induced disease severity.

Full Text

Duke Authors

Cited Authors

  • Mantri, CK; Soundarajan, G; Saron, WAA; Rathore, APS; Alonso, S; St John, AL

Published Date

  • May 12, 2021

Published In

Volume / Issue

  • 13 / 5

PubMed ID

  • 34066286

Pubmed Central ID

  • PMC8152039

Electronic International Standard Serial Number (EISSN)

  • 1999-4915

Digital Object Identifier (DOI)

  • 10.3390/v13050900

Language

  • eng

Conference Location

  • Switzerland