Antibody signatures against viruses and microbiome reflect past and chronic exposures and associate with aging and inflammation

Sergio Andreu-Sánchez; Aida Ripoll-Cladellas; Anna Culinscaia; Ozlem Bulut; Arno R Bourgonje; Mihai G Netea; Peter Lansdorp; Geraldine Aubert; Marc Jan Bonder; Lude Franke; Thomas Vogl; Monique G P van der Wijst; Marta Melé; Debbie Van Baarle; Jingyuan Fu; Alexandra Zhernakova

doi:10.1016/j.isci.2024.109981

Antibody signatures against viruses and microbiome reflect past and chronic exposures and associate with aging and inflammation

iScience. 2024 May 16;27(6):109981. doi: 10.1016/j.isci.2024.109981. eCollection 2024 Jun 21.

Authors

Sergio Andreu-Sánchez^{1

2}, Aida Ripoll-Cladellas³, Anna Culinscaia¹, Ozlem Bulut⁴, Arno R Bourgonje^{5

6}, Mihai G Netea^{4

7}, Peter Lansdorp^{8

9}, Geraldine Aubert^{8

10}, Marc Jan Bonder¹, Lude Franke¹, Thomas Vogl¹¹, Monique G P van der Wijst¹, Marta Melé³, Debbie Van Baarle¹², Jingyuan Fu^{1

2}, Alexandra Zhernakova¹

Affiliations

¹ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
² Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³ Life Sciences Department, Barcelona Supercomputing Center, 08034 Barcelona, Catalonia, Spain.
⁴ Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, the Netherlands.
⁵ Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁶ The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
⁷ Department for Immunology & Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
⁸ Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, BC, Canada.
⁹ Departments of Hematology and Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
¹⁰ Repeat Diagnostics Inc, Vancouver, BC, Canada.
¹¹ Center for Cancer Research, Medical University of Vienna, Wien, Austria.
¹² Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Abstract

Encounters with pathogens and other molecules can imprint long-lasting effects on our immune system, influencing future physiological outcomes. Given the wide range of microbes to which humans are exposed, their collective impact on health is not fully understood. To explore relations between exposures and biological aging and inflammation, we profiled an antibody-binding repertoire against 2,815 microbial, viral, and environmental peptides in a population cohort of 1,443 participants. Utilizing antibody-binding as a proxy for past exposures, we investigated their impact on biological aging, cell composition, and inflammation. Immune response against cytomegalovirus (CMV), rhinovirus, and gut bacteria relates with telomere length. Single-cell expression measurements identified an effect of CMV infection on the transcriptional landscape of subpopulations of CD8 and CD4 T-cells. This examination of the relationship between microbial exposures and biological aging and inflammation highlights a role for chronic infections (CMV and Epstein-Barr virus) and common pathogens (rhinoviruses and adenovirus C).

Keywords: Genomics; Immunology; Proteomics.