Journal article
Anti-IL-15 treatment reduces acute lentivirus inflammation and signaling in the brain
Cell reports. Medicine, Vol.7(1), 102567
01/20/2025
DOI: 10.1016/j.xcrm.2025.102567
PMID: 41519130
Abstract
HIV-associated neurocognitive disorder (HAND) remains a significant complication in people living with HIV, with inflammation playing a central role in its pathogenesis. Understanding how the brain’s immune network responds to lentiviral infection is therefore critical. We show that acute simian immunodeficiency virus (SIV) infection elicits a robust resident brain immune response in control animals, marked by enhanced microglial ramification. In contrast, animals pretreated with anti-interleukin (IL)-15 antibodies (αIL-15) before SIVmac239X infection display reduced neuroinflammation without altering brain viral burden. Peripheral IL-15 blockade decreases brain-infiltrating T lymphocytes, alters their spatial dynamics, suppresses proinflammatory cytokine (IL-6) expression in microglia, and increases anti-inflammatory cytokine (TGF-β) expression in brain macrophages. Transcriptomic profiling reveals a global reduction in inflammatory signaling and an upregulation of genes associated with M1 macrophage pathways. Together, these findings demonstrate that peripheral IL-15 modulation attenuates neuroinflammation during acute lentiviral infection and highlight IL-15 as a potential therapeutic target for neuroinflammatory conditions of the brain.
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•Peripheral pre-administration of αIL-15 alters CNS immune responses to acute SIV infection•T cell quantities in the brain are reduced following peripheral αIL-15•Pre-treatment with αIL-15 prior to SIV infection does not alter brain viral load•Blood IL-15 quantities and elevated T cells are linked to M2 microglia phenotype in brain
Ram and Gopalakrishnan et al. demonstrate that peripheral cytokine modulation alters the brain’s inflammatory environment and immune response to retroviral infection. These results demonstrate that a favorable central nervous system environment can be induced by intravenous administrations of antibodies. This work will inform and guide therapeutic strategies for HIV-associated neurocognitive disorder.
Details
- Title: Subtitle
- Anti-IL-15 treatment reduces acute lentivirus inflammation and signaling in the brain
- Creators
- Daniel R. Ram - Beth Israel Deaconess Medical CenterRaja Mohan Gopalakrishnan - Beth Israel Deaconess Medical CenterMalika Aid - Beth Israel Deaconess Medical CenterKyle Kroll - Duke UniversityJasmine Miftahof - University of IowaOmar Aristizabal - University of IowaEunice Kayitare Gikundiro - Beth Israel Deaconess Medical CenterCaitlin Davis - Beth Israel Deaconess Medical CenterMarco M. Hefti - University of IowaKimberly L. Fiock - University of IowaBrook Tilahun - Beth Israel Deaconess Medical CenterYvette Umutoniwase - Beth Israel Deaconess Medical CenterKate Loidolt - Beth Israel Deaconess Medical CenterChristine M. Fennessey - Frederick National Laboratory for Cancer ResearchNoe B. Mercado - Beth Israel Deaconess Medical CenterVictoria Harper-Alexander - University of Central FloridaRhianna Jones - Duke UniversityGriffin Woolley - Duke UniversityValerie Varner - Beth Israel Deaconess Medical CenterMichelle Lifton - Beth Israel Deaconess Medical CenterSteven E. Bosinger - Emory UniversityDan H. Barouch - Beth Israel Deaconess Medical CenterBrandon F. Keele - Frederick National Laboratory for Cancer ResearchR. Keith Reeves - Beth Israel Deaconess Medical CenterC. Sabrina Tan - Beth Israel Deaconess Medical Center
- Resource Type
- Journal article
- Publication Details
- Cell reports. Medicine, Vol.7(1), 102567
- DOI
- 10.1016/j.xcrm.2025.102567
- PMID
- 41519130
- NLM abbreviation
- Cell Rep Med
- ISSN
- 2666-3791
- eISSN
- 2666-3791
- Publisher
- Elsevier Inc
- Language
- English
- Electronic publication date
- 01/09/2026
- Date published
- 01/20/2025
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Pathology; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9985121503002771
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