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Aging dysregulates neutrophil extracellular trap formation in response to HIV in blood and genital tissues

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 neutro...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10684664/
https://www.ncbi.nlm.nih.gov/pubmed/38035114
http://dx.doi.org/10.3389/fimmu.2023.1256182
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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
author_facet 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
author_sort Moreno de Lara, Laura
collection PubMed
description 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.
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spelling pubmed-106846642023-11-30 Aging dysregulates neutrophil extracellular trap formation in response to HIV in blood and genital tissues 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 Front Immunol Immunology 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. Frontiers Media S.A. 2023-11-15 /pmc/articles/PMC10684664/ /pubmed/38035114 http://dx.doi.org/10.3389/fimmu.2023.1256182 Text en Copyright © 2023 Moreno de Lara, Werner, Borchers, Carrillo-Salinas, Marmol, Parthasarathy, Iyer, Vogell, Illanes, Abadía-Molina, Ochsenbauer, Wira and Rodriguez-Garcia https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
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
Aging dysregulates neutrophil extracellular trap formation in response to HIV in blood and genital tissues
title Aging dysregulates neutrophil extracellular trap formation in response to HIV in blood and genital tissues
title_full Aging dysregulates neutrophil extracellular trap formation in response to HIV in blood and genital tissues
title_fullStr Aging dysregulates neutrophil extracellular trap formation in response to HIV in blood and genital tissues
title_full_unstemmed Aging dysregulates neutrophil extracellular trap formation in response to HIV in blood and genital tissues
title_short Aging dysregulates neutrophil extracellular trap formation in response to HIV in blood and genital tissues
title_sort aging dysregulates neutrophil extracellular trap formation in response to hiv in blood and genital tissues
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10684664/
https://www.ncbi.nlm.nih.gov/pubmed/38035114
http://dx.doi.org/10.3389/fimmu.2023.1256182
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