Toll-Like Receptor Signaling in Severe Acute Respiratory Syndrome Coronavirus 2-Induced Innate Immune Responses and the Potential Application Value of Toll-Like Receptor Immunomodulators in Patients With Coronavirus Disease 2019

Jiayu Dai; Yibo Wang; Hongrui Wang; Ziyuan Gao; Ying Wang; Mingli Fang; Shuyou Shi; Peng Zhang; Hua Wang; Yingying Su; Ming Yang

doi:10.3389/fmicb.2022.948770

Toll-Like Receptor Signaling in Severe Acute Respiratory Syndrome Coronavirus 2-Induced Innate Immune Responses and the Potential Application Value of Toll-Like Receptor Immunomodulators in Patients With Coronavirus Disease 2019

Front Microbiol. 2022 Jun 27:13:948770. doi: 10.3389/fmicb.2022.948770. eCollection 2022.

Authors

Jiayu Dai^{1

2}, Yibo Wang^{1

2}, Hongrui Wang¹, Ziyuan Gao^{1

2}, Ying Wang^{1

2}, Mingli Fang¹, Shuyou Shi¹, Peng Zhang³, Hua Wang¹, Yingying Su⁴, Ming Yang¹

Affiliations

¹ Department of Molecular Biology, College of Basic Medical Sciences, Jilin University, Changchun, China.
² College of Clinical Medicine, Jilin University, Changchun, China.
³ Department of Thoracic Surgery, The First Affiliated Hospital of Jilin University, Changchun, China.
⁴ Department of Anatomy, College of Basic Medical Sciences, Jilin University, Jilin, China.

Abstract

Toll-like receptors (TLRs) are key sensors that recognize the pathogen-associated molecular patterns (PAMPs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to activate innate immune response to clear the invading virus. However, dysregulated immune responses may elicit the overproduction of proinflammatory cytokines and chemokines, resulting in the enhancement of immune-mediated pathology. Therefore, a proper understanding of the interaction between SARS-CoV-2 and TLR-induced immune responses is very important for the development of effective preventive and therapeutic strategies. In this review, we discuss the recognition of SARS-CoV-2 components by TLRs and the downstream signaling pathways that are activated, as well as the dual role of TLRs in regulating antiviral effects and excessive inflammatory responses in patients with coronavirus disease 2019 (COVID-19). In addition, this article describes recent progress in the development of TLR immunomodulators including the agonists and antagonists, as vaccine adjuvants or agents used to treat hyperinflammatory responses during SARS-CoV-2 infection.

Keywords: COVID-19; SARS-CoV-2; Toll-like receptor; immunomodulator; innate immune response.

Publication types

Review