Neil McElligott

South Texas Veterans Health Care System

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David Feldman

Cadence Design Systems (United States)

David Schmit

Saarland University

Austin C. Lawler

South Texas Veterans Health Care System

Renee L. Reichelderfer

South Texas Veterans Health Care System

Sally Grassmuck

South Texas Veterans Health Care System

Emily Wang

The University of Texas MD Anderson Cancer Center

Kimberly Oakman

South Texas Veterans Health Care System

Lauren Villegas

South Texas Veterans Health Care System

Valeria Orrù

Institute of Genetic and Biomedical Research

Brian K. Agan

Uniformed Services University of the Health Sciences

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South Texas Veterans Health Care System

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The University of Texas Health Science Center at San Antonio

The University of Texas Health Science Center at Houston

The University of Texas at San Antonio

Foundation for Advancing Veterans Health Research

Audie L. Murphy Memorial VA Hospital

United States Department of Veterans Affairs

Murphy Oil Corporation (United States)

University of California, San Diego

University Health System

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Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection

Nature Communications (2023)

Sunil K. Ahuja Muthu Saravanan Manoharan Grace C. Lee Lyle R. McKinnon Justin A. Meunier

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.

Immunocompetence

Stressor

10.1038/s41467-023-38238-6

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Immunologic resilience and COVID-19 survival advantage

Journal of Allergy and Clinical Immunology (2021)

Grace C. Lee Marcos I. Restrepo Nathan Harper Muthu Saravanan Manoharan Alisha M. Smith

The risk of severe coronavirus disease 2019 (COVID-19) varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR).

10.1016/j.jaci.2021.08.021

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Citations (35)