Enduring echoes: Post-infectious long-term changes in innate immunity

Elisabeth A Dulfer; Leo A B Joosten; Mihai G Netea

doi:10.1016/j.ejim.2023.12.020

Enduring echoes: Post-infectious long-term changes in innate immunity

Eur J Intern Med. 2023 Dec 21:S0953-6205(23)00456-9. doi: 10.1016/j.ejim.2023.12.020. Online ahead of print.

Authors

Elisabeth A Dulfer¹, Leo A B Joosten², Mihai G Netea³

Affiliations

¹ Department of Internal Medicine, Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, the Netherlands. Electronic address: elisabeth.dulfer@radboudumc.nl.
² Department of Internal Medicine, Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, the Netherlands; Department of Medical Genetics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
³ Department of Internal Medicine, Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, the Netherlands; Department for Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Germany.

PMID: 38135583
DOI: 10.1016/j.ejim.2023.12.020

Abstract

Upon encountering pathogens, the immune system typically responds by initiating an acute and self-limiting reaction, with symptoms subsiding after the pathogen has been cleared. However, long-term post-infectious clinical symptoms can manifest months or even years after the initial infection. 'Trained immunity', the functional reprogramming of innate immune cells through epigenetic and metabolic rewiring, has been proposed as a key concept for understanding these long-term effects. Although trained immunity can result in enhanced protection against reinfection with heterologous pathogens, it can also contribute to detrimental outcomes. Persisting and excessive inflammation can cause tissue damage and aggravate immune-mediated conditions and cardiovascular complications. On the other hand, suppression of immune cell effector functions by long-lasting epigenetic changes can result in post-infectious immune paralysis. Distinct stimuli can evoke different trained immunity programs, potentially resulting in different consequences for the host. In this review, we provide an overview of both the adaptive and maladaptive consequences of infectious diseases. We discuss how long-term immune dysregulation in patients can be addressed by tailoring host-directed interventions and identify areas of scientific and therapeutic potential to advance further.

Keywords: Infectious diseases; Innate immunity; Post-infectious complications; Trained immunity.

Publication types

Review