Immune cell phenotyping frequently detects lineage-unrelated receptors. Here, we report that surface receptors can be transferred from primary macrophages to CD4 T cells and identify the Fcγ receptor CD32 as driver and cargo of this trogocytotic transfer. Filamentous CD32+ nanoprotrusions deposit distinct plasma membrane patches onto target T cells. Transferred receptors confer cell migration and adhesion properties, and macrophage-derived membrane patches render resting CD4 T cells susceptible to infection by serving as hotspots for HIV-1 binding. Antibodies that recognize T cell epitopes enhance CD32-mediated trogocytosis. Such autoreactive anti-HIV-1 envelope antibodies can be found in the blood of HIV-1 patients and, consistently, the percentage of CD32+ CD4 T cells is increased in their blood. This CD32-mediated, antigen-independent cell communication mode transiently expands the receptor repertoire and functionality of immune cells. HIV-1 hijacks this mechanism by triggering the generation of trogocytosis-promoting autoantibodies to gain access to immune cells critical to its persistence.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Elevated counts of alveolar macrophages and attenuated phagocytic capacity are associated with chronic obstructive pulmonary disease (COPD). Factors governing macrophage phagocytosis are poorly understood. In this study we aimed to compare the influence of airway epithelial cell secretions from individuals with COPD and without COPD (non-COPD) on macrophage phagocytic activity, and the role of antimicrobial peptides (AMPs).
Supernatants from non-COPD and COPD small airway epithelial cell (SAEC) cultures exposed to non-typeable Haemophilus influenzae (NTHi) were applied to human monocyte-derived macrophages (MDMs) to assess their influence on phagocytosis. SAECs were analysed for changes in AMP expression by quantitative reverse transcription PCR, and the influence of select AMPs on macrophage phenotype and function was assessed by flow cytometry and metabolic activity assay.
Secretions from the apical and basolateral surface of NTHi-exposed SAECs from non-COPD donors elicited superior phagocytic capacity in MDMs. Moreover, NTHi exposure led to a rapid increase in the expression of a range of AMPs by non-COPD SAECs, but this response was delayed in COPD SAECs. We demonstrate that treatment with AMPs β-defensin 2 and S100 calcium binding protein A8/S100 calcium binding protein A9 (S100A8/A9) improved the phagocytic capacity of MDMs. In-depth analysis of the influence of S100A8/A9 on MDMs revealed a role for this AMP in macrophage phenotype and function. Furthermore, we show that the expression of S100A8 and S100A9 is directly regulated by WNT/β-catenin signalling, a known deregulated pathway in COPD.
In conclusion, for the first time, we demonstrate that airway epithelium from patients with COPD has a reduced capacity to support the phagocytic function of macrophages in response to acute NTHi exposure, and we identify the WNT/β-catenin signalling-modulated and epithelium-derived S100A8/A9 as a potent regulator of macrophage phenotype and function.
Copyright ©The authors 2022.