Bacterial targeting of the neutrophil inhibitory receptor LILRB3 to evade antibody immunity
File(s)
Article in press
Author(s)
Rumpret, Matevž
Lewis Marffy, Alexander L
Zhang, Ying
van Woudenbergh, Esther
van der Lans, Sjors PA
Type
Journal Article
Abstract
Antibody-mediated responses are critical for antibacterial immunity, driving Fc receptor-mediated phagocytosis, respiratory burst, and bacterial killing. Inhibitory immune receptors regulate cellular activation and immune homoeostasis, but whether they are targeted to evade antibody-mediated responses is unclear. Here, we show that the highly expressed inhibitory LILRB3 receptor on neutrophils is targeted by Streptococcus agalactiae to suppress antibody-driven defence. We show that the surface-localised β protein of S. agalactiae bound to LILRB3 and induced its cross-linking. β and LILRB3 interactions suppressed Fc receptor-mediated antibacterial responses such as respiratory burst and bacterial killing, inhibiting antibody-dependent bacterial killing by neutrophils. Moreover, β expression and LILRB3 targeting are associated with S. agalactiae lineages that cause invasive diseases in older adults, indicating that targeting inhibitory receptors most likely provides an immune evasion mechanism when antibody responses are waning, such as in immunocompromised or elderly individuals. Altogether, these results highlight a simple and important mechanism that bacterial pathogens utilise to overcome effective antibody-driven phagocyte responses.
Date Issued
2026-06-11
Date Acceptance
2026-05-27
Citation
Nature Communications, 2026
ISSN
2041-1723
Publisher
Nature Portfolio
Journal / Book Title
Nature Communications
Copyright Statement
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1038/s41467-026-74098-6
Publication Status
Published online
Date Publish Online
2026-06-11