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

Autor:	Moreno de Lara L; Department of Immunology, Tufts University School of Medicine, Boston, MA, United States.; Instituto de Biopatología y Medicina Regenerativa, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain., Werner A; Department of Immunology, Tufts University School of Medicine, Boston, MA, United States., Borchers A; Department of Immunology, Tufts University School of Medicine, Boston, MA, United States., Carrillo-Salinas FJ; Department of Immunology, Tufts University School of Medicine, Boston, MA, United States., Marmol W; Program in Genetics, Molecular, and Cellular Biology, Tufts University School of Medicine, Boston, MA, United States., Parthasarathy S; Department of Immunology, Tufts University School of Medicine, Boston, MA, United States., Iyer V; Department of Gynecology and Obstetrics, Tufts Medical Center, Boston, MA, United States., Vogell A; Department of Gynecology and Obstetrics, Tufts Medical Center, Boston, MA, United States., Illanes D; Department of Gynecology and Obstetrics, Tufts Medical Center, Boston, MA, United States., Abadía-Molina AC; Instituto de Biopatología y Medicina Regenerativa, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain.; Departamento de Bioquímica y Biología Molecular 3 e Inmunología, Universidad de Granada, Granada, Spain., Ochsenbauer C; Department of Medicine and UAB Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL, United States., Wira CR; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States., Rodriguez-Garcia M; Department of Immunology, Tufts University School of Medicine, Boston, MA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Nov 15; Vol. 14, pp. 1256182. Date of Electronic Publication: 2023 Nov 15 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1256182
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Moreno de Lara, Werner, Borchers, Carrillo-Salinas, Marmol, Parthasarathy, Iyer, Vogell, Illanes, Abadía-Molina, Ochsenbauer, Wira and Rodriguez-Garcia.)
Databáze:	MEDLINE
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