Neu1 deficiency and fibrotic lymph node microenvironment lead to imbalance in M1/M2 macrophage polarization
Year: 2024
Type: article
Abstract: Macrophages play a pivotal role in tissue homeostasis, pathogen defense, and inflammation resolution. M1 and M2 macrophage phenotypes represent two faces in a spectrum of responses to microenvironmental changes, crucial in both physiological and pathological conditions. Neuraminidase 1 (Neu1), a lysosomal and cell surface sialidase responsible for removing terminal sialic acid residues from glycoconjugates, modulates several macrophage functions, including phagocytosis and Toll-like receptor (TLR) signaling. Current evidence suggests that Neu1 expression influences M1/M2 macrophage phenotype alterations in the context of cardiovascular diseases, indicating a potential role for Neu1 in macrophage polarization. For this reason, we investigated the impact of Neu1 deficiency on macrophage polarization in vitro and in vivo. Using bone marrow-derived macrophages (BMDMs) and peritoneal macrophages from Neu1 knockout (Neu1−/−) mice and wild-type (WT) littermate controls, we demonstrated that Neu1-deficient macrophages exhibit an aberrant M2-like phenotype, characterized by elevated macrophage mannose receptor 1 (MMR/CD206) expression and reduced responsiveness to M1 stimuli. This M2-like phenotype was also observed in vivo in peritoneal and splenic macrophages. However, lymph node (LN) macrophages from Neu1−/− mice exhibited phenotypic alterations with reduced CD206 expression. Further analysis revealed that peripheral LNs from Neu1−/− mice were highly fibrotic, with overexpression of transforming growth factor-beta 1 (TGF-β1) and hyperactivated TGF-β signaling in LN macrophages. Consistently, TGF-β1 was found to alter M1/M2 macrophage polarization in vitro. Our findings showed that Neu1 deficiency prompts macrophages towards an M2 phenotype and that microenvironmental changes, particularly increased TGF-β1 in fibrotic tissues such as peripheral LNs in Neu1−/− mice, further influence M1/M2 macrophage polarization, highlighting its sensitivity to the local microenvironment. Therapeutic interventions targeting Neu1 or TGF-β signaling pathways may offer the potential to regulate macrophage behavior across different diseases.
Source: Frontiers in Immunology
Institution: Universidad Autónoma de Chile
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,295
Awards: ROLE OF LYSOSOMAL SIALIDASE NEU1 IN MENINGEAL LYMPHATIC VASCULATURE DYSFUNCTION AND NEUROINFLAMMATION, NEURAMINIDASE 1 MODULATES M1/M2 POLARIZATION OF MICROGLIA/CNS-INFILTRATED MACROPHAGES CONTRIBUTING TO MULTIPLE SCLEROSIS PATHOGENESIS, ROLE OF MENINGEAL LYMPHATIC VASCULATURE IN THE DEVELOPMENT OF PSYCHIATRIC DISORDERS AND NEUROINFLAMMATION TRIGGERED BY OBESITY-ASSOCIATED DYSBIOSIS", ROLE OF MENINGEAL LYMPHATIC ENDOTHELIAL CELL-SECRETED REELIN IN THE MODULATION OF MENINGEAL MACROPHAGE POLARIZATION AND NEUROINFLAMMATION DURING SIALIDOSIS
OpenAlex ID: W4402529664