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

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 re...

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Published in:	Nature communications Vol. 14; no. 1; pp. 3286 - 31
Main Authors:	Ahuja, Sunil K., Manoharan, Muthu Saravanan, Lee, Grace C., McKinnon, Lyle R., Meunier, Justin A., Steri, Maristella, Harper, Nathan, Fiorillo, Edoardo, Smith, Alisha M., Restrepo, Marcos I., Branum, Anne P., Bottomley, Matthew J., Orrù, Valeria, Jimenez, Fabio, Carrillo, Andrew, Pandranki, Lavanya, Winter, Caitlyn A., Winter, Lauryn A., Gaitan, Alvaro A., Moreira, Alvaro G., Walter, Elizabeth A., Silvestri, Guido, King, Christopher L., Zheng, Yong-Tang, Zheng, Hong-Yi, Kimani, Joshua, Blake Ball, T., Plummer, Francis A., Fowke, Keith R., Harden, Paul N., Wood, Kathryn J., Ferris, Martin T., Lund, Jennifer M., Heise, Mark T., Garrett, Nigel, Canady, Kristen R., Abdool Karim, Salim S., Little, Susan J., Gianella, Sara, Smith, Davey M., Letendre, Scott, Richman, Douglas D., Cucca, Francesco, Trinh, Hanh, Sanchez-Reilly, Sandra, Hecht, Joan M., Cadena Zuluaga, Jose A., Anzueto, Antonio, Pugh, Jacqueline A., Agan, Brian K., Root-Bernstein, Robert, Clark, Robert A., Okulicz, Jason F., He, Weijing
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 13-06-2023 Nature Publishing Group Nature Portfolio
Subjects:	13/21 13/31 14/1 38/39 38/61 38/90 38/91 631/250/254 631/337/2019 64/110 692/499 692/699/255 Aging Biomarkers CD4 antigen CD8 antigen COVID-19 Degradation Disease control Disease resistance Female Gene expression HIV Human immunodeficiency virus Humanities and Social Sciences Humans Immunocompetence Infectious diseases Inflammation Life span Longevity Lymphocytes T multidisciplinary Outcome Assessment, Health Care Peripheral blood Recurrent infection Resilience Science Science (multidisciplinary) Sepsis Sexually transmitted diseases Skin cancer STD
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Summary:	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. The response to infectious and inflammatory challenges differs among people but the reasons for this are poorly understood. Here the authors explore the impact of variables such as age, sex, and the capacity for controlling inflammation and maintaining immunocompetence, linking this capacity to favourable health outcomes and lifespan.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-023-38238-6