Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition

Author:

Tal Michal Caspi12,Torrez Dulgeroff Laughing Bear12,Myers Lara3,Cham Lamin B.4,Mayer-Barber Katrin D.5,Bohrer Andrea C.5,Castro Ehydel5,Yiu Ying Ying12,Lopez Angel Cesar6,Pham Ed67,Carmody Aaron B.8,Messer Ronald J.3,Gars Eric9,Kortmann Jens10,Markovic Maxim12,Hasenkrug Michaela3,Peterson Karin E.3,Winkler Clayton W.3,Woods Tyson A.3,Hansen Paige12,Galloway Sarah12,Wagh Dhananjay1112,Fram Benjamin J.7,Nguyen Thai7,Corey Daniel12,Kalluru Raja Sab9,Banaei Niaz9,Rajadas Jayakumar121314,Monack Denise M.6,Ahmed Aijaz7,Sahoo Debashis1516,Davis Mark M.6,Glenn Jeffrey S.67,Adomati Tom4,Lang Karl S.4,Weissman Irving L.12,Hasenkrug Kim J.3ORCID

Affiliation:

1. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA

2. Ludwig Cancer Center, Stanford University School of Medicine, Stanford, California, USA

3. Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA

4. Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany

5. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

6. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA

7. Department of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA

8. Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA

9. Department of Pathology, Stanford University School of Medicine, Stanford, California, USA

10. Genentech Inc., South San Francisco, California, USA

11. Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, California, USA

12. Biomaterials and Advanced Drug Delivery Laboratory, Cardio Vascular Institute, Stanford University School of Medicine, Stanford, California, USA

13. Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University School of Medicine, Stanford, California, USA

14. Bioengineering and Therapeutic Sciences, UCSF School of Pharmacy, University of California, San Francisco, San Francisco, California, USA

15. Department of Pediatrics, University of California, San Diego, La Jolla, California, USA

16. Department of Computer Science and Engineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, California, USA

Abstract

Immune responses to infectious agents are initiated when a pathogen or its components bind to pattern recognition receptors (PRRs). PRR binding sets off a cascade of events that activates immune responses. We now show that, in addition to activating immune responses, PRR signaling also initiates an immunosuppressive response, probably to limit inflammation. The importance of the current findings is that blockade of immunomodulatory signaling, which is mediated by the upregulation of the CD47 molecule, can lead to enhanced immune responses to any pathogen that triggers PRR signaling. Since most or all pathogens trigger PRRs, CD47 blockade could be used to speed up and strengthen both innate and adaptive immune responses when medically indicated. Such immunotherapy could be done without a requirement for knowing the HLA type of the individual, the specific antigens of the pathogen, or, in the case of bacterial infections, the antimicrobial resistance profile.

Funder

HHS | NIH | National Cancer Institute

HHS | National Institutes of Health

HHS | NIH | National Institute of Allergy and Infectious Diseases

Division of Intramural Research, National Institute of Allergy and Infectious Diseases

HHS | NIH | National Heart, Lung, and Blood Institute

Bay Area Lyme Foundation

Virginia and D.K. Ludwig Fund for Cancer Research

Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation

Stanford University

SU | School of Medicine, Stanford University

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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