Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection
Abstract
Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 13, 2023
- Source ID
- 10.1038/s41467-023-38238-6
Entities
People
- Aamir Ehsan
- Ali Jabur
- Alisha M. Smith
- Alvaro A. Gaitan
- Alvaro G. Moreira
- Andrea Yunes
- Andreia Williamson
- Andrew Carrillo
- Andrew Wallace
- Aneela N. Hussain
- Angel Louder
- Angela Birdwell
- Anjuli Vasquez
- Anna R. Tyler
- Anne P. Branum
- Anoop Nambiar
- Antonio Anzueto
- Audrey Haywood
- Austin C. Lawler
- Brande Harris
- Brian K. Agan
- Caitlyn A. Winter
- Cecilia Hinojosa
- Celida Martinez
- Chadwick S. Lester
- Charlotte Murray
- Charmaine Mainor
- Cheryl Padgett
- Chloe Mata
- Christopher L King
- Claudio Solorzano
- Corina Escamilla
- Daniel Nassery
- Davey M. Smith
- David Feldman
- David Schmit
- Deborah Baruch-bienen
- Debra Flores
- Delvina Ford
- Diego Maselli
- Douglas D. Richman
- Edoardo Fiorillo
- Edward J. Tovar
- Elizabeth A. Walter
- Emily Wang
- Evan M. Renz
- Fabio Jimenez
- Francesco Cucca
- Francis A. Plummer
- Grace C. Lee
- Graciela L. Perez
- Gregory Anstead
- Guido Silvestri
- Haidee V. Lewis
- Hanh Trinh
- Heather Briggs
- Hong-yi Zheng
- Jacqueline A. Pugh
- Jane O’rorke
- Jason F. Okulicz
- Jeanette Ross
- Jennifer Barker
- Jennifer Gomez
- Jennifer J. Dacus
- Jennifer M Lund
- Jessica Garcia
- Jill Dickerson
- Joan M. Hecht
- Joanna D. Foy
- Joanna Moreno
- Jollynn Doanne
- Jorge A. Villalpando
- Jose A. Cadena Zuluaga
- Joseph Agnew
- Joshua Hanson
- Joshua Kimani
- Judith M. Corral
- Julianne Flynn
- Julie Muetz
- Justin A. Meunier
- Katharine H. Zentner
- Kathleen Morneau
- Kathryn J. Wood
- Keith R. Fowke
- Kevin C. Proud
- Kevin C. Schindler
- Kimberly Oakman
- Kristen R. Canady
- Kristy J. Preston
- Laura Medlin
- Lauren Villegas
- Lauryn A. Winter
- Lavanya Pandranki
- Lyle R. Mckinnon
- Lynn L. Horvath
- Marcos I. Restrepo
- Maria C. Veloso
- Maria E. Sanchez
- Maria Wallace
- Marichu Balmes
- Marisa Patterson
- Maristella Steri
- Maritza Garza
- Mark T Heise
- Martin T Ferris
- Matthew J Bottomley
- Megan Freeman
- Megan Walker
- Melanie Goel
- Melissa Villanueva
- Michael A. Pomager
- Michelle Rangel
- Miguel Escalante
- Mohamed I. Abdalla
- Monica Lee
- Muthu Saravanan Manoharan
- Myra Mireles
- Nathan Harper
- Neil Mcelligott
- Nigel Garrett
- Nilam Soni
- Pamela Jewell
- Patrick B. Polk
- Patrick J. Danaher
- Paul N. Harden
- Rachel Maldonado
- Raj T. Sehgal
- Renee L. Reichelderfer
- Robert A Clark
- Robert E. Phillips
- Robert Farrar
- Robert Nathanson
- Robert Root-Bernstein
- Rogelio Perez
- Rogelio Perez Iii
- Sadie A. Trammell Velasquez
- Saleem Ali
- Salim Abdool Karim
- Sally Grassmuck
- Samantha Elbel
- Samantha Galley
- Samuel B. Munro
- Sandra G. Adams
- Sandra Sanchez-reilly
- Sara Gianella
- Scott A. Depaul
- Scott Letendre
- Sergi Pascual-guardia
- Sherraine Gilman
- South Texas Veterans Health Care System Covid-19 Team
- Stacy Braddy
- Stephanie M. Levine
- Stephanie Wickizer
- Stephen Bradford
- Steven G. Venticinque
- Sunil K. Ahuja
- Susan Grigsby
- Susan J Little
- T. Blake Ball
- Tammy Sanders
- Temple A. Ratcliffe
- Teresa Rudd
- Teri Hopkins
- Thomas B. Johnson
- Tony T. Ho
- Valeria Orrù
- Valerie Escamilla
- Varun K. Goyal
- Velma Bible
- Weijing He
- Win S. Tam
- Yemi Adebayo
- Yong-Tang Zheng
- Yvette Martinez
Organizations
- National Institute of Allergy and Infectious Diseases
- National Institute on Aging
- United States Air Force
- United States Department of Health and Human Services
- United States Department of Veterans Affairs