UMMS Affiliation
Department of Medicine, Division of Cardiovascular Medicine; Department of Medicine, Division of Infectious Disease and Immunology
Publication Date
2019-04-16
Document Type
Article
Disciplines
Cardiology | Cardiovascular Diseases | Cells | Fluids and Secretions | Hemic and Immune Systems | Immunity | Immunology of Infectious Disease | Immunopathology | Infectious Disease | Influenza Humans | Respiratory Tract Diseases | Virus Diseases
Abstract
Influenza infection increases the incidence of myocardial infarction but the reason is unknown. Platelets mediate vascular occlusion through thrombotic functions but are also recognized to have immunomodulatory activity. To determine if platelet processes are activated during influenza infection, we collected blood from 18 patients with acute influenza infection. Microscopy reveals activated platelets, many containing viral particles and extracellular-DNA associated with platelets. To understand the mechanism, we isolate human platelets and treat them with influenza A virus. Viral-engulfment leads to C3 release from platelets as a function of TLR7 and C3 leads to neutrophil-DNA release and aggregation. TLR7 specificity is confirmed in murine models lacking the receptor, and platelet depletion models support platelet-mediated C3 and neutrophil-DNA release post-influenza infection. These findings demonstrate that the initial intrinsic defense against influenza is mediated by platelet-neutrophil cross-communication that tightly regulates host immune and complement responses but can also lead to thrombotic vascular occlusion.
Keywords
influenza, influenza infection, platelets, myocardial infarction
Rights and Permissions
Copyright © The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
10.1038/s41467-019-09607-x
Source
Nat Commun. 2019 Apr 16;10(1):1780. doi: 10.1038/s41467-019-09607-x. Link to article on publisher's site
Journal/Book/Conference Title
Nature communications
Related Resources
PubMed ID
30992428
Repository Citation
Koupenova-Zamor, Milka; Corkrey, Heather A.; Vitseva, Olga; Manni, Giorgia; Pang, Catherine J.; Clancy, Lauren; Yao, Chen; Rade, Jeffrey J.; Levy, Daniel; Wang, Jennifer P.; Finberg, Robert W.; Kurt-Jones, Evelyn A.; and Freedman, Jane E., "The role of platelets in mediating a response to human influenza infection" (2019). Open Access Articles. 3836.
https://escholarship.umassmed.edu/oapubs/3836
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Cardiology Commons, Cardiovascular Diseases Commons, Cells Commons, Fluids and Secretions Commons, Hemic and Immune Systems Commons, Immunity Commons, Immunology of Infectious Disease Commons, Immunopathology Commons, Infectious Disease Commons, Influenza Humans Commons, Respiratory Tract Diseases Commons, Virus Diseases Commons