CD3+ Macrophages Deliver Proinflammatory Cytokines by a CD3- and Transmembrane TNF-Dependent Pathway and Are Increased at the BCG-Infection Site

Abstract

Macrophages are essential cells of the innate immune response against microbial infections, and they have the ability to adapt under both pro- and anti-inflammatory conditions and develop different functions. A growing body of evidence regarding a novel macrophage subpopulation that expresses CD3 has recently emerged. Here, we explain that human circulating monocytes can be differentiated into CD3+TCRαβ+ and CD3+TCRαβ− macrophages. Both cell subpopulations express on their cell surface HLA family molecules, but only the CD3+TCRαβ+ macrophage subpopulation co-express CD1 family molecules and transmembrane TNF (tmTNF). CD3+TCRαβ+ macrophages secrete IL-1β, IL-6 IP-10, and MCP-1 by both tmTNF- and CD3-dependent pathways, while CD3+TCRαβ− macrophages specifically produce IFN-γ, TNF, and MIP-1β by a CD3-dependent pathway. In this study, we also used a mouse model of BCG-induced pleurisy and demonstrated that CD3+ myeloid cells (TCRαβ+ and TCRαβ− cells) are increased at the infection sites during the acute phase (2 weeks post-infection). Interestingly, cell increment was mediated by tmTNF, and the soluble form of TNF was dispensable. BCG-infection also induced the expression of TNF receptor 2 on CD3+ myeloid cells, which increased after BCG-infection, suggesting that the tmTNF/TNFRs axis plays an important role in the presence or function of these cells in tuberculosis.

Simvastatin Therapy Attenuates Memory Deficits that Associate with Brain Monocyte Infiltration in Chronic Hypercholesterolemia

“…Similar to CD69, hydralazine but not simvastatin increased monocyte and macrophage CD3 expression ( Fig.S4 ), which has been shown to involve in the delivery of pro-inflammatory cytokines (i.e. TNF-α) by macrophages (Rodriguez-Cruz et al, 2019). Pro-inflammatory cytokine profiling in THP-1 cells revealed that LPS-induced augmentation of TNF-α protein expression only reversed with simvastatin but not hydralazine (Fig.6C).…”

Tumour-Infiltrating Lymphocytes (TILs) and PD-L1 Expression Correlate with Lymph Node Metastasis, High-Grade Transformation and Shorter Metastasis-Free Survival in Patients with Acinic Cell Carcinoma (AciCC) of the Salivary Glands

“…Cancer cell antigens are captured by dendritic cells and presented on MHCI and MHCII molecules to T cells [ 42 ]. Moreover, there are CD3+ subpopulations of macrophages, that have the ability to present antigens to other cells [ 43 ]. The recognition of cancer antigens results in the priming and activation of effector T cell responses in the lymph nodes.…”

Flow Cytometry: From Experimental Design to Its Application in the Diagnosis and Monitoring of Respiratory Diseases

“…The use of FCM has also allowed the identification of non-classical cell populations such as monocytes and macrophages that express the CD3/TCR αβ complex in response to mycobacterial infections. This cell population increases both at the systemic level and at the site of infection; apparently its presence is regulated by a TNF-dependent pathway, carrying out phagocytosis processes, and they are an important source of pro-inflammatory cytokines [ 73 , 74 , 75 ]. The increase in this cell population suggests that its frequency can be monitored in TB patients as a biomarker, showing the relevance of the use of FCM in the search for new markers of cell function in the context of TB.…”