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

Autor: Mantri CK; Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore., Soundarajan G; Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore., Saron WAA; Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore., Rathore APS; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA., Alonso S; Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore 119077, Singapore., St John AL; Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore 119077, Singapore.; SingHealth Duke-National University of Singapore Global Health Institute, Singapore 168753, Singapore.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2021 May 12; Vol. 13 (5). Date of Electronic Publication: 2021 May 12.
DOI: 10.3390/v13050900
Abstrakt: 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.
Databáze: MEDLINE
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