NK cells at the crossroads in COVID-19: a question of timing

Susana del Toro-Arreola; Fabiola Solorzano-Ibarra; Martha C. Téllez-Bañuelos; Jesse Haramati

doi:10.36829/63CTS.v7i3.975

Autores/as

Susana del Toro-Arreola Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara http://orcid.org/0000-0003-4120-6796
Fabiola Solorzano-Ibarra Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara http://orcid.org/0000-0002-4675-2203
Martha C. Téllez-Bañuelos Centro Universitario de Ciencias, Biológicas y Agropecuarias, Universidad de Guadalajara http://orcid.org/0000-0002-9057-1397
Jesse Haramati Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara http://orcid.org/0000-0003-4120-6796

DOI:

https://doi.org/10.36829/63CTS.v7i3.975

Resumen

The outbreak of the novel coronavirus SARS-CoV-2 and the attendant physiological symptoms associated with the COVID-19 disease have led to an explosion of interest studying different aspects of the immune response. As of yet, the particular roles of natural killer cells are not well understood in this disease. NK cells are critical first-response cytotoxic cells of the innate immune system. NK cells are traditionally considered important for their roles in innate immunity against tumors and viral infected cells, as well as their ability to produce cytokines, particularly interferon-?, and participate in antibody dependent cell cytotoxicity (ADCC). Here, we describe the role of NK cells in peripheral blood and in the lungs with respect to the pathology caused by SARS-CoV-2 and discuss the implications of proposed different types of therapies on NK cells. Evidence is accumulating that NK cells play an important role in initial surveillance as part of innate immunity. With the progression of the disease and rising inflammation, these cells, when in circulation, appear to become exhausted and ineffective. In the COVID lung, however, a complex interplay between inflammatory cells, chemokines, cytokines and aberrantly activated migratory NK cells occurs, potentiating local inflammation and the critical situation in the lungs.

Descargas

Los datos de descargas todavía no están disponibles.

Biografía del autor/a

Susana del Toro-Arreola, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara

Instituto de Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara; Laboratorio de Inmunología, Departamento de Fisiología

Fabiola Solorzano-Ibarra, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara

Instituto de Enfermedades Crónico
Degenerativas, Departamento de Biología Molecular y Genómica

Martha C. Téllez-Bañuelos, Centro Universitario de Ciencias, Biológicas y Agropecuarias, Universidad de Guadalajara

Laboratorio de Inmunobiología, Departamento de Biología Celular y Molecular

Jesse Haramati, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara

Laboratorio de Inmunobiología, Departamento de Biología Celular y Molecular

Citas

R. Lu et al., Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395, 565-574 (2020).

B. Oberfeld et al., SnapShot: COVID-19. Cell 181, 954-954.e951 (2020).

CDC.gov. (https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html), vol. 2020.

K. K. To et al., Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis 20, 565-574 (2020).

C. Qin et al., Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis, (2020).

M. Arentz et al., Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA, (2020).

P. K. Bhatraju et al., Covid-19 in Critically Ill Patients in the Seattle Region - Case Series. N Engl J Med 382, 2012-2022 (2020).

Y. Wang et al., Clinical Characteristics of Patients Infected With the Novel 2019 Coronavirus (SARS-Cov-2) in Guangzhou, China. Open Forum Infect Dis 7, ofaa187 (2020).

E. J. Giamarellos-Bourboulis et al., Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure. Cell Host Microbe 27, 992-1000.e1003 (2020).

M. Tan et al., Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China. Immunology 160, 261-268 (2020).

A. Jurado et al., COVID-19: age, Interleukin-6, C-Reactive Protein and lymphocytes as key clues from a multicentre retrospective study in Spain. medRxiv, 2020.2005.2013.20101345 (2020).

J. C. Spurrell, S. Wiehler, R. S. Zaheer, S. P. Sanders, D. Proud, Human airway epithelial cells produce IP-10 (CXCL10) in vitro and in vivo upon rhinovirus infection. Am J Physiol Lung Cell Mol Physiol 289, L85-95 (2005).

R. Tokunaga et al., CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation - A target for novel cancer therapy. Cancer Treat Rev 63, 40-47 (2018).

X. Zeng et al., IP-10 mediates selective mononuclear cell accumulation and activation in response to intrapulmonary transgenic expression and during adenovirus-induced pulmonary inflammation. J Interferon Cytokine Res 25, 103-112 (2005).

A. G. Laing et al., A consensus Covid-19 immune signature combines immuno-protection with discrete sepsis-like traits associated with poor prognosis. medRxiv, 2020.2006.2008.20125112 (2020).

S. Varchetta et al., Unique Immunological Profile In Patients With COVID-19. (2020).

H. Shi et al., The inhibition of IL-2/IL-2R gives rise to CD8. Cell Death Dis 11, 429 (2020).

C. Maucourant et al., Natural killer cell activation related to clinical outcome of COVID-19. medRxiv, 2020.2007.2007.20148478 (2020).

A. Marcos-Jimenez et al., Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19. medRxiv, 2020.2006.2015.20131706 (2020).

A. J. Wilk et al., A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat Med 26, 1070-1076 (2020).

V. Bordoni et al., An inflammatory profile correlates with decreased frequency of cytotoxic cells in COVID-19. Clin Infect Dis, (2020).

L. Cifaldi et al., Inhibition of natural killer cell cytotoxicity by interleukin-6: implications for the pathogenesis of macrophage activation syndrome. Arthritis Rheumatol 67, 3037-3046 (2015).

A. Mazzoni et al., Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent. J Clin Invest, (2020).

B. Diao et al., Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front Immunol 11, 827 (2020).

H. Y. Zheng et al., Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell Mol Immunol 17, 541-543 (2020).

S. Pesce et al., Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization. J Allergy Clin Immunol 139, 335-346.e333 (2017).

M. Zheng et al., Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol 17, 533-535 (2020).

A. Yaqinuddin, J. Kashir, Innate immunity in COVID-19 patients mediated by NKG2A receptors, and potential treatment using Monalizumab, Cholroquine, and antiviral agents. Med Hypotheses 140, 109777 (2020).

J. Wu et al., IL-6 and IL-8 secreted by tumour cells impair the function of NK cells via the STAT3 pathway in oesophageal squamous cell carcinoma. J Exp Clin Cancer Res 38, 321 (2019).

Y. Wu, Z. Tian, H. Wei, Developmental and Functional Control of Natural Killer Cells by Cytokines. Front Immunol 8, 930 (2017).

M. S. Osman, C. van Eeden, J. W. Cohen Tervaert, Fatal COVID-19 infections: Is NK cell dysfunction a link with autoimmune HLH? Autoimmun Rev 19, 102561 (2020).

N. A. Arreygue-Garcia et al., Augmented serum level of major histocompatibility complex class I-related chain A (MICA) protein and reduced NKG2D expression on NK and T cells in patients with cervical cancer and precursor lesions. BMC Cancer 8, 16 (2008).

D. Pinto et al., Structural and functional analysis of a potent sarbecovirus neutralizing antibody. bioRxiv, (2020).

A. N. Akbar, D. W. Gilroy, Aging immunity may exacerbate COVID-19. Science 369, 256-257 (2020).

J. Campisi, Cellular Senescence and Lung Function during Aging. Yin and Yang. Ann Am Thorac Soc 13 Suppl 5, S402-S406 (2016).

L. Cunningham, P. Simmonds, I. Kimber, D. A. Basketter, J. P. McFadden, Perforin and resistance to SARS coronavirus 2. J Allergy Clin Immunol 146, 52-53 (2020).

C. Rosat Consiglio et al., The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19. medRxiv, 2020.2007.2008.20148353 (2020).

J. Cong, H. Wei, Natural Killer Cells in the Lungs. Front Immunol 10, 1416 (2019).

B. W. Robinson, P. Pinkston, R. G. Crystal, Natural killer cells are present in the normal human lung but are functionally impotent. J Clin Invest 74, 942-950 (1984).

M. Balsamo et al., Hypoxia downregulates the expression of activating receptors involved in NK-cell-mediated target cell killing without affecting ADCC. Eur J Immunol 43, 2756-2764 (2013).

G. E. Cooper, K. Ostridge, S. I. Khakoo, T. M. A. Wilkinson, K. J. Staples, Human CD49a. Front Immunol 9, 1671 (2018).

M. F. Abdul-Careem et al., Critical role of natural killer cells in lung immunopathology during influenza infection in mice. J Infect Dis 206, 167-177 (2012).

P. Kumar, M. S. Thakar, W. Ouyang, S. Malarkannan, IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection. Mucosal Immunol 6, 69-82 (2013).

J. P. Mooney et al., Natural Killer Cells Dampen the Pathogenic Features of Recall Responses to Influenza Infection. Front Immunol 11, 135 (2020).

F. Gong et al., Interleukin-22 Might Act as a Double-Edged Sword in Type 2 Diabetes and Coronary Artery Disease. Mediators Inflamm 2016, 8254797 (2016).

D. Blanco-Melo et al., Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell 181, 1036-1045.e1039 (2020).

M. Liao et al., Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med 26, 842-844 (2020).

S. P. Sajuthi et al., Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium. bioRxiv, (2020).

Z. Zhou et al., Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients. Cell Host Microbe 27, 883-890.e882 (2020).

R. L. Chua et al., Cross-talk between the airway epithelium and activated immune cells defines severity in COVID-19. medRxiv, 2020.2004.2029.20084327 (2020).

L. Antonioli, M. Fornai, C. Pellegrini, C. Blandizzi, NKG2A and COVID-19: another brick in the wall. Cell Mol Immunol 17, 672-674 (2020).

J. J. Fu, K. J. Baines, L. G. Wood, P. G. Gibson, Systemic inflammation is associated with differential gene expression and airway neutrophilia in asthma. OMICS 17, 187-199 (2013).

S. W. Mateer et al., IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murine Models of Colitis. Am J Pathol 188, 1625-1639 (2018).

W. Almishri et al., TNF? Augments Cytokine-Induced NK Cell IFN? Production through TNFR2. Journal of innate immunity 8, 617-629 (2016).

E. I. Azhar, D. S. C. Hui, Z. A. Memish, C. Drosten, A. Zumla, The Middle East Respiratory Syndrome (MERS). Infect Dis Clin North Am 33, 891-905 (2019).

C. T. Tseng, L. A. Perrone, H. Zhu, S. Makino, C. J. Peters, Severe acute respiratory syndrome and the innate immune responses: modulation of effector cell function without productive infection. J Immunol 174, 7977-7985 (2005).

S. Ivanov et al., Interleukin-22 reduces lung inflammation during influenza A virus infection and protects against secondary bacterial infection. J Virol 87, 6911-6924 (2013).

P. H. G. Duijf, Baseline pulmonary levels of CD8+ T cells and NK cells inversely correlate with expression of the SARS-CoV-2 entry receptor ACE2. bioRxiv, (2020).

M. Market et al., Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies. Front Immunol 11, 1512 (2020).

M. Benucci et al., COVID-19 pneumonia treated with Sarilumab: A clinical series of eight patients. Journal of medical virology, 10.1002/jmv.26062 (2020).

B. K. Patterson et al., Disruption of the CCL5/RANTES-CCR5 Pathway Restores Immune Homeostasis and Reduces Plasma Viral Load in Critical COVID-19. medRxiv, 2020.2005.2002.20084673 (2020).

G. De Luca et al., GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study. The Lancet Rheumatology.

F. Cantini et al., Baricitinib therapy in COVID-19: A pilot study on safety and clinical impact. J Infect, (2020).

P. Horby et al., Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med, (2020).

S. Di Cosimo et al., Immune checkpoint inhibitors: a physiology-driven approach to the treatment of coronavirus disease 2019. Eur J Cancer 135, 62-65 (2020).

M. Prete, E. Favoino, G. Catacchio, V. Racanelli, F. Perosa, SARS-CoV-2 infection complicated by inflammatory syndrome. Could high-dose human immunoglobulin for intravenous use (IVIG) be beneficial? Autoimmunity reviews 19, 102559-102559 (2020).

X. Ge, C. R. Li, J. Yang, G. B. Wang, Aberrantly decreased levels of NKG2D expression in children with kawasaki disease. Scand J Immunol 77, 389-397 (2013).

H. K. Kandikattu, S. U. Venkateshaiah, S. Kumar, A. Mishra, IL-15 immunotherapy is a viable strategy for COVID-19. Cytokine Growth Factor Rev, (2020).

T. Venkataraman, M. B. Frieman, The role of epidermal growth factor receptor (EGFR) signaling in SARS coronavirus-induced pulmonary fibrosis. Antiviral Res 143, 142-150 (2017).

D. Acharya, G. Liu, M. U. Gack, Dysregulation of type I interferon responses in COVID-19. Nat Rev Immunol 20, 397-398 (2020).

R. Channappanavar et al., IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes. J Clin Invest 129, 3625-3639 (2019).

P. Luo et al., Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis. Am J Trop Med Hyg 103, 69-72 (2020).

P. L. Semple et al., Induction of granulysin and perforin cytolytic mediator expression in 10-week-old infants vaccinated with BCG at birth. Clin Dev Immunol 2011, 438463 (2011).

S. Suliman et al., Bacillus Calmette-Guérin (BCG) Revaccination of Adults with Latent Mycobacterium tuberculosis Infection Induces Long-Lived BCG-Reactive NK Cell Responses. Journal of immunology (Baltimore, Md. : 1950) 197, 1100-1110 (2016).