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Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition
It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as well as an activating component. We now show that the very early innate response also has an immunosuppressive component. Infected cells upregulate the CD47 “don’t eat me” sign...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315125/ https://www.ncbi.nlm.nih.gov/pubmed/32576678 http://dx.doi.org/10.1128/mBio.01293-20 |
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author | Tal, Michal Caspi Torrez Dulgeroff, Laughing Bear Myers, Lara Cham, Lamin B. Mayer-Barber, Katrin D. Bohrer, Andrea C. Castro, Ehydel Yiu, Ying Ying Lopez Angel, Cesar Pham, Ed Carmody, Aaron B. Messer, Ronald J. Gars, Eric Kortmann, Jens Markovic, Maxim Hasenkrug, Michaela Peterson, Karin E. Winkler, Clayton W. Woods, Tyson A. Hansen, Paige Galloway, Sarah Wagh, Dhananjay Fram, Benjamin J. Nguyen, Thai Corey, Daniel Kalluru, Raja Sab Banaei, Niaz Rajadas, Jayakumar Monack, Denise M. Ahmed, Aijaz Sahoo, Debashis Davis, Mark M. Glenn, Jeffrey S. Adomati, Tom Lang, Karl S. Weissman, Irving L. Hasenkrug, Kim J. |
author_facet | Tal, Michal Caspi Torrez Dulgeroff, Laughing Bear Myers, Lara Cham, Lamin B. Mayer-Barber, Katrin D. Bohrer, Andrea C. Castro, Ehydel Yiu, Ying Ying Lopez Angel, Cesar Pham, Ed Carmody, Aaron B. Messer, Ronald J. Gars, Eric Kortmann, Jens Markovic, Maxim Hasenkrug, Michaela Peterson, Karin E. Winkler, Clayton W. Woods, Tyson A. Hansen, Paige Galloway, Sarah Wagh, Dhananjay Fram, Benjamin J. Nguyen, Thai Corey, Daniel Kalluru, Raja Sab Banaei, Niaz Rajadas, Jayakumar Monack, Denise M. Ahmed, Aijaz Sahoo, Debashis Davis, Mark M. Glenn, Jeffrey S. Adomati, Tom Lang, Karl S. Weissman, Irving L. Hasenkrug, Kim J. |
author_sort | Tal, Michal Caspi |
collection | PubMed |
description | It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as well as an activating component. We now show that the very early innate response also has an immunosuppressive component. Infected cells upregulate the CD47 “don’t eat me” signal, which slows the phagocytic uptake of dying and viable cells as well as downstream antigen-presenting cell (APC) functions. A CD47 mimic that acts as an essential virulence factor is encoded by all poxviruses, but CD47 expression on infected cells was found to be upregulated even by pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that encode no mimic. CD47 upregulation was revealed to be a host response induced by the stimulation of both endosomal and cytosolic pathogen recognition receptors (PRRs). Furthermore, proinflammatory cytokines, including those found in the plasma of hepatitis C patients, upregulated CD47 on uninfected dendritic cells, thereby linking innate modulation with downstream adaptive immune responses. Indeed, results from antibody-mediated CD47 blockade experiments as well as CD47 knockout mice revealed an immunosuppressive role for CD47 during infections with lymphocytic choriomeningitis virus and Mycobacterium tuberculosis. Since CD47 blockade operates at the level of pattern recognition receptors rather than at a pathogen or antigen-specific level, these findings identify CD47 as a novel potential immunotherapeutic target for the enhancement of immune responses to a broad range of infectious agents. |
format | Online Article Text |
id | pubmed-7315125 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-73151252020-06-25 Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition Tal, Michal Caspi Torrez Dulgeroff, Laughing Bear Myers, Lara Cham, Lamin B. Mayer-Barber, Katrin D. Bohrer, Andrea C. Castro, Ehydel Yiu, Ying Ying Lopez Angel, Cesar Pham, Ed Carmody, Aaron B. Messer, Ronald J. Gars, Eric Kortmann, Jens Markovic, Maxim Hasenkrug, Michaela Peterson, Karin E. Winkler, Clayton W. Woods, Tyson A. Hansen, Paige Galloway, Sarah Wagh, Dhananjay Fram, Benjamin J. Nguyen, Thai Corey, Daniel Kalluru, Raja Sab Banaei, Niaz Rajadas, Jayakumar Monack, Denise M. Ahmed, Aijaz Sahoo, Debashis Davis, Mark M. Glenn, Jeffrey S. Adomati, Tom Lang, Karl S. Weissman, Irving L. Hasenkrug, Kim J. mBio Research Article It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as well as an activating component. We now show that the very early innate response also has an immunosuppressive component. Infected cells upregulate the CD47 “don’t eat me” signal, which slows the phagocytic uptake of dying and viable cells as well as downstream antigen-presenting cell (APC) functions. A CD47 mimic that acts as an essential virulence factor is encoded by all poxviruses, but CD47 expression on infected cells was found to be upregulated even by pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that encode no mimic. CD47 upregulation was revealed to be a host response induced by the stimulation of both endosomal and cytosolic pathogen recognition receptors (PRRs). Furthermore, proinflammatory cytokines, including those found in the plasma of hepatitis C patients, upregulated CD47 on uninfected dendritic cells, thereby linking innate modulation with downstream adaptive immune responses. Indeed, results from antibody-mediated CD47 blockade experiments as well as CD47 knockout mice revealed an immunosuppressive role for CD47 during infections with lymphocytic choriomeningitis virus and Mycobacterium tuberculosis. Since CD47 blockade operates at the level of pattern recognition receptors rather than at a pathogen or antigen-specific level, these findings identify CD47 as a novel potential immunotherapeutic target for the enhancement of immune responses to a broad range of infectious agents. American Society for Microbiology 2020-06-23 /pmc/articles/PMC7315125/ /pubmed/32576678 http://dx.doi.org/10.1128/mBio.01293-20 Text en https://doi.org/10.1128/AuthorWarrantyLicense.v1 This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. |
spellingShingle | Research Article Tal, Michal Caspi Torrez Dulgeroff, Laughing Bear Myers, Lara Cham, Lamin B. Mayer-Barber, Katrin D. Bohrer, Andrea C. Castro, Ehydel Yiu, Ying Ying Lopez Angel, Cesar Pham, Ed Carmody, Aaron B. Messer, Ronald J. Gars, Eric Kortmann, Jens Markovic, Maxim Hasenkrug, Michaela Peterson, Karin E. Winkler, Clayton W. Woods, Tyson A. Hansen, Paige Galloway, Sarah Wagh, Dhananjay Fram, Benjamin J. Nguyen, Thai Corey, Daniel Kalluru, Raja Sab Banaei, Niaz Rajadas, Jayakumar Monack, Denise M. Ahmed, Aijaz Sahoo, Debashis Davis, Mark M. Glenn, Jeffrey S. Adomati, Tom Lang, Karl S. Weissman, Irving L. Hasenkrug, Kim J. Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition |
title | Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition |
title_full | Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition |
title_fullStr | Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition |
title_full_unstemmed | Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition |
title_short | Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition |
title_sort | upregulation of cd47 is a host checkpoint response to pathogen recognition |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315125/ https://www.ncbi.nlm.nih.gov/pubmed/32576678 http://dx.doi.org/10.1128/mBio.01293-20 |
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