Aging dysregulates neutrophil extracellular trap formation in response to HIV in blood and genital tissues
-
Published:2023-11-15
Issue:
Volume:14
Page:
-
ISSN:1664-3224
-
Container-title:Frontiers in Immunology
-
language:
-
Short-container-title:Front. Immunol.
Author:
Moreno de Lara Laura,Werner Alexandra,Borchers Anna,Carrillo-Salinas Francisco J.,Marmol Wendelin,Parthasarathy Siddharth,Iyer Vidya,Vogell Alison,Illanes Diego,Abadía-Molina Ana C.,Ochsenbauer Christina,Wira Charles R.,Rodriguez-Garcia Marta
Abstract
Women acquire HIV through sexual transmission, with increasing incidence in women >50 years old. Identifying protective mechanisms in the female genital tract (FGT) is important to prevent HIV-acquisition in women as they age. Human genital and blood neutrophils inactivate HIV by releasing neutrophil extracellular traps (NETs), an innate protective mechanism against HIV-infection. However, how NET formation is triggered by HIV in different tissues and whether this mechanism is affected by aging remain unknown. We demonstrate that the mechanisms that trigger NET release in response to HIV are different in blood and genital tissues, and that NET release decreases with aging. In blood neutrophils, HIV stimulation independently activated calcium pathways and endosomal TLR8, but aging reduced calcium responses, resulting in delayed NET release. In contrast, calcium responses were absent in genital neutrophils and NET release was triggered preferentially through TLR8 activation, but aging impaired this pathway. HIV induced NET formation through non-lytic pathways in blood and FGT neutrophils, except for a small subset of NETs that incorporated annexin V and lactoferrin predominantly in blood, suggesting proinflammatory and lytic NET release. Our findings demonstrate that blood neutrophils cannot model genital neutrophil responses which has important implications to understanding protection against HIV acquisition.
Funder
National Institutes of Health
Publisher
Frontiers Media SA
Subject
Immunology,Immunology and Allergy
Reference62 articles.
1. Global HIV & AIDS statistics2021
2. HIV - Key facts2022
3. Diagnoses of HIV infection in the United States and dependent areas 2019 [HIV Surveillance Report2021
4. Prevalence of HIV and chronic comorbidities among older adults;Negin;AIDS,2012
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献