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Middle east respiratory syndrome corona virus spike glycoprotein suppresses macrophage responses via DPP4-mediated induction of IRAK-M and PPARγ.
Oncotarget. 2017 Feb 07; 8(6):9053-9066.O

Abstract

Middle East Respiratory Syndrome Corona Virus (MERS-CoV) is transmitted via the respiratory tract and causes severe Acute Respiratory Distress Syndrome by infecting lung epithelial cells and macrophages. Macrophages can readily recognize the virus and eliminate it. MERS-CoV infects cells via its Spike (S) glycoprotein that binds on Dipeptidyl-Peptidase 4 (DPP4) receptor present on macrophages. Whether this Spike/DPP4 association affects macrophage responses remains unknown. Herein we demonstrated that infection of macrophages with lentiviral particles pseudotyped with MERS-CoV S glycoprotein results in suppression of macrophage responses since it reduced the capacity of macrophages to produce TNFα and IL-6 in naive and LPS-activated THP-1 macrophages and augmented LPS-induced production of the immunosuppressive cytokine IL-10. MERS-CoV S glycoprotein induced the expression of the negative regulator of TLR signaling IRAK-M as well as of the transcriptional repressor PPARγ. Inhibition of DPP4 by its inhibitor sitagliptin or siRNA abrogated the effects of MERS-CoV S glycoprotein on IRAK-M, PPARγ and IL-10, confirming that its immunosuppressive effects were mediated by DPP4 receptor. The effect was observed both in THP-1 macrophages and human primary peripheral blood monocytes. These findings support a DPP4-mediated suppressive action of MERS-CoV in macrophages and suggest a potential target for effective elimination of its pathogenicity.

Links

Publisher Full Text
ncbi.nlm.nih.gov
oncotarget.com
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Authors+Show Affiliations

Al-Qahtani AA
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Center, Saudi Arabia. Department of Microbiology and Immunology, School of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Lyroni K
Laboratory of Clinical Chemistry, Medical School, University of Crete, Heraklion, Greece.
Aznaourova M
Laboratory of Clinical Chemistry, Medical School, University of Crete, Heraklion, Greece.
Tseliou M
Laboratory of Virology, Medical School, University of Crete, Heraklion, Greece.
Al-Anazi MR
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Center, Saudi Arabia.
Al-Ahdal MN
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Center, Saudi Arabia. Department of Microbiology and Immunology, School of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Alkahtani S
Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia.
Sourvinos G
Laboratory of Virology, Medical School, University of Crete, Heraklion, Greece.
Tsatsanis C
Laboratory of Clinical Chemistry, Medical School, University of Crete, Heraklion, Greece.

MeSH

Dipeptidyl Peptidase 4Dipeptidyl-Peptidase IV InhibitorsHost-Pathogen InteractionsHumansInterleukin-1 Receptor-Associated KinasesInterleukin-10Interleukin-6Macrophage ActivationMacrophagesMiddle East Respiratory Syndrome CoronavirusPPAR gammaRNA InterferenceSignal TransductionSpike Glycoprotein, CoronavirusTHP-1 CellsTransfectionTumor Necrosis Factor-alpha

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28118607

Citation

Al-Qahtani, Ahmed A., et al. "Middle East Respiratory Syndrome Corona Virus Spike Glycoprotein Suppresses Macrophage Responses Via DPP4-mediated Induction of IRAK-M and PPARγ." Oncotarget, vol. 8, no. 6, 2017, pp. 9053-9066.
Al-Qahtani AA, Lyroni K, Aznaourova M, et al. Middle east respiratory syndrome corona virus spike glycoprotein suppresses macrophage responses via DPP4-mediated induction of IRAK-M and PPARγ. Oncotarget. 2017;8(6):9053-9066.
Al-Qahtani, A. A., Lyroni, K., Aznaourova, M., Tseliou, M., Al-Anazi, M. R., Al-Ahdal, M. N., Alkahtani, S., Sourvinos, G., & Tsatsanis, C. (2017). Middle east respiratory syndrome corona virus spike glycoprotein suppresses macrophage responses via DPP4-mediated induction of IRAK-M and PPARγ. Oncotarget, 8(6), 9053-9066. https://doi.org/10.18632/oncotarget.14754
Al-Qahtani AA, et al. Middle East Respiratory Syndrome Corona Virus Spike Glycoprotein Suppresses Macrophage Responses Via DPP4-mediated Induction of IRAK-M and PPARγ. Oncotarget. 2017 Feb 7;8(6):9053-9066. PubMed PMID: 28118607.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Middle east respiratory syndrome corona virus spike glycoprotein suppresses macrophage responses via DPP4-mediated induction of IRAK-M and PPARγ. AU - Al-Qahtani,Ahmed A, AU - Lyroni,Konstantina, AU - Aznaourova,Marina, AU - Tseliou,Melpomeni, AU - Al-Anazi,Mashael R, AU - Al-Ahdal,Mohammed N, AU - Alkahtani,Saad, AU - Sourvinos,George, AU - Tsatsanis,Christos, PY - 2016/07/22/received PY - 2017/01/10/accepted PY - 2017/1/25/pubmed PY - 2018/2/27/medline PY - 2017/1/25/entrez KW - DPP4 KW - IRAK-M KW - Immune response KW - Immunity KW - Immunology and Microbiology Section KW - MERS CoV KW - cytokines KW - macrophages SP - 9053 EP - 9066 JF - Oncotarget JO - Oncotarget VL - 8 IS - 6 N2 - Middle East Respiratory Syndrome Corona Virus (MERS-CoV) is transmitted via the respiratory tract and causes severe Acute Respiratory Distress Syndrome by infecting lung epithelial cells and macrophages. Macrophages can readily recognize the virus and eliminate it. MERS-CoV infects cells via its Spike (S) glycoprotein that binds on Dipeptidyl-Peptidase 4 (DPP4) receptor present on macrophages. Whether this Spike/DPP4 association affects macrophage responses remains unknown. Herein we demonstrated that infection of macrophages with lentiviral particles pseudotyped with MERS-CoV S glycoprotein results in suppression of macrophage responses since it reduced the capacity of macrophages to produce TNFα and IL-6 in naive and LPS-activated THP-1 macrophages and augmented LPS-induced production of the immunosuppressive cytokine IL-10. MERS-CoV S glycoprotein induced the expression of the negative regulator of TLR signaling IRAK-M as well as of the transcriptional repressor PPARγ. Inhibition of DPP4 by its inhibitor sitagliptin or siRNA abrogated the effects of MERS-CoV S glycoprotein on IRAK-M, PPARγ and IL-10, confirming that its immunosuppressive effects were mediated by DPP4 receptor. The effect was observed both in THP-1 macrophages and human primary peripheral blood monocytes. These findings support a DPP4-mediated suppressive action of MERS-CoV in macrophages and suggest a potential target for effective elimination of its pathogenicity. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/28118607/Middle_east_respiratory_syndrome_corona_virus_spike_glycoprotein_suppresses_macrophage_responses_via_DPP4_mediated_induction_of_IRAK_M_and_PPARγ_ L2 - https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.14754 DB - PRIME DP - Unbound Medicine ER -