Mechanistic Understanding of Innate and Adaptive Immune Responses in SARS-CoV-2 Infection

Overview

Journal Mol Immunol

Specialties Allergy & Immunology
Molecular Biology

Date 2021 May 3

PMID 33940513

Citations 7

Authors

Mumtaz Y Balkhi

Affiliations

Soon will be listed here.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered global pandemic that continue to impact adversely human health. New understanding has emerged about the innate and adaptive immune responses elicited in SARS-CoV-2 infection. The understanding of innate immune responses generated in hosts early in SARS-CoV-2 infection is vital for treatment efforts. Antiviral cytokines are released by innate immune cells in response to viral infections that play a pivotal role in limiting viral replication, pathology and generating optimal adaptive immune responses alongside the long-term memory responses against reinfections. One aspect of innate immune response generated against SARS-CoV-2 in vivo and which has received much attention has been high proinflammatory cytokine release in COVID-19 patients. Another vital discovery has been that the antiviral cytokine type I Interferon (IFN) family IFN-α mediates upregulation of angiotensin converting enzyme 2 (ACE2) membrane protein in airway epithelial cells. ACE2 is a receptor that SARS-CoV-2 binds to infect host cells. New understanding has emerged about the mechanism of SARS-CoV-2 induced exaggerated proinflammatory cytokine release as well as transcriptional regulation of ACE2. This review discusses various mechanisms underlying SARS-CoV-2 induced exaggerated proinflammatory cytokine response as well as transcriptional regulation of ACE2 receptor. We further elaborate on adaptive and memory responses generated against SARS-CoV-2.

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References

Wrapp D, Wang N, Corbett K, Goldsmith J, Hsieh C, Abiona O . Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020; 367(6483):1260-1263. PMC: 7164637. DOI: 10.1126/science.abb2507. View

Honda K, Yanai H, Mizutani T, Negishi H, Shimada N, Suzuki N . Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling. Proc Natl Acad Sci U S A. 2004; 101(43):15416-21. PMC: 523464. DOI: 10.1073/pnas.0406933101. View

Trouillet-Assant S, Viel S, Gaymard A, Pons S, Richard J, Perret M . Type I IFN immunoprofiling in COVID-19 patients. J Allergy Clin Immunol. 2020; 146(1):206-208.e2. PMC: 7189845. DOI: 10.1016/j.jaci.2020.04.029. View

Grant R, Morales-Nebreda L, Markov N, Swaminathan S, Querrey M, Guzman E . Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia. Nature. 2021; 590(7847):635-641. PMC: 7987233. DOI: 10.1038/s41586-020-03148-w. View

Li S, Zhang Y, Guan Z, Li H, Ye M, Chen X . SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation. Signal Transduct Target Ther. 2020; 5(1):235. PMC: 7545816. DOI: 10.1038/s41392-020-00334-0. View

Barrett D, Teachey D, Grupp S . Toxicity management for patients receiving novel T-cell engaging therapies. Curr Opin Pediatr. 2013; 26(1):43-9. PMC: 4198063. DOI: 10.1097/MOP.0000000000000043. View

Suthar M, Zimmerman M, Kauffman R, Mantus G, Linderman S, Hudson W . Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients. Cell Rep Med. 2020; 1(3):100040. PMC: 7276302. DOI: 10.1016/j.xcrm.2020.100040. View

Ahmed R, Gray D . Immunological memory and protective immunity: understanding their relation. Science. 1996; 272(5258):54-60. DOI: 10.1126/science.272.5258.54. View

Feldstein L, Rose E, Horwitz S, Collins J, Newhams M, Son M . Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med. 2020; 383(4):334-346. PMC: 7346765. DOI: 10.1056/NEJMoa2021680. View

10.

Lin B, Ferguson C, White J, Wang S, Vessella R, True L . Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2. Cancer Res. 1999; 59(17):4180-4. View

11.

Kato H, Sugimura T, Akagi T, Sato N, Hashino K, Maeno Y . Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients. Circulation. 1996; 94(6):1379-85. DOI: 10.1161/01.cir.94.6.1379. View

12.

Graham R, Kyogoku C, Sigurdsson S, Vlasova I, Davies L, Baechler E . Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus. Proc Natl Acad Sci U S A. 2007; 104(16):6758-63. PMC: 1847749. DOI: 10.1073/pnas.0701266104. View

13.

Gray J, Westerhof L, MacLeod M . The roles of resident, central and effector memory CD4 T-cells in protective immunity following infection or vaccination. Immunology. 2018; . PMC: 6050220. DOI: 10.1111/imm.12929. View

14.

Wykes M, Pombo A, Jenkins C, MacPherson G . Dendritic cells interact directly with naive B lymphocytes to transfer antigen and initiate class switching in a primary T-dependent response. J Immunol. 1998; 161(3):1313-9. View

15.

Davila M, Riviere I, Wang X, Bartido S, Park J, Curran K . Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014; 6(224):224ra25. PMC: 4684949. DOI: 10.1126/scitranslmed.3008226. View

16.

Liu G, Lee J, Parker Z, Acharya D, Chiang J, van Gent M . ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity. Nat Microbiol. 2021; 6(4):467-478. PMC: 8103894. DOI: 10.1038/s41564-021-00884-1. View

17.

Bennett S, Carbone F, Karamalis F, Flavell R, Miller J, Heath W . Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature. 1998; 393(6684):478-80. DOI: 10.1038/30996. View

18.

Banchereau J, Steinman R . Dendritic cells and the control of immunity. Nature. 1998; 392(6673):245-52. DOI: 10.1038/32588. View

19.

Yao X, Li T, He Z, Ping Y, Liu H, Yu S . [A pathological report of three COVID-19 cases by minimal invasive autopsies]. Zhonghua Bing Li Xue Za Zhi. 2020; 49(5):411-417. DOI: 10.3760/cma.j.cn112151-20200312-00193. View

20.

Mercer J, Schelhaas M, Helenius A . Virus entry by endocytosis. Annu Rev Biochem. 2010; 79:803-33. DOI: 10.1146/annurev-biochem-060208-104626. View