Inhibiting Retinoic Acid Signaling in Dendritic Cells Suppresses Respiratory Syncytial Virus Infection Through Enhanced Antiviral Immunity

Overview

Journal iScience

Publisher Cell Press

Date 2024 Jul 24

PMID 39045100

Authors

Mohammad Farazuddin

Grant Acker

Joseph Zourob

Jessica J OKonek

Pamela T Wong

Susan Morris

Andrew J Rasky

Chang H Kim

Nicholas W Lukacs

James R Baker Jr

Affiliations

Soon will be listed here.

Abstract

Retinoic acid (RA), controls the immunoregulatory functions of many immune cells, including dendritic cells (DCs), and is important for mucosal immunity. In DCs, RA regulates the expression of pattern recognition receptors and stimulates interferon production. Here, we investigated the role of RA in DCs in mounting immunity to respiratory syncytial virus (RSV). To abolish RA signaling in DCs, we used mice expressing a dominant negative form of retinoic acid receptor-α (RARα) under the CD11c promoter (CD11c-dnRARα). Paradoxically, upon RSV challenge, these animals had lower viral burden, reduced pathology, and greater Th1 polarized immunity than wild-type (WT) mice. Moreover, CD11c-dnRARα DCs infected with RSV showed enhancement in innate and adaptive immunity genes, while genes associated with viral replication were downregulated. These findings suggest that the absence of RA signaling in DCs enhances innate immunity against RSV infection leading to decreased viral load and reduced pathogenicity.

Citing Articles

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Liang M, Dong Q, Wu W, Fan J Clin Rev Allergy Immunol. 2025; 68(1):8.

PMID: 39873814 DOI: 10.1007/s12016-024-09018-x.

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