An Essential Role for TAGLN2 in Phagocytosis of Lipopolysaccharide-activated Macrophages

Abstract

Activated macrophages have a greater ability of phagocytosis against pathogens that is mediated by large-scale actin rearrangement. However, molecular machineries that conduct this task have not been fully identified. Here, we demonstrate an unanticipated role of TAGLN2, a 22-kDa actin-binding protein, in Toll-like receptor (TLR)-stimulated phagocytosis. TAGLN2 was greatly induced in macrophages in response to lipopolysaccharide (LPS), a ligand for TLR4, partly via the NF-κB pathway. TAGLN2-deficient macrophages (TAGLN2 −/−) showed defective phagocytic functions of IgM- and IgG-coated sheep red blood cells as well as bacteria. Cell signaling pathways involved in actin rearrangement—PI3 kinase/AKT and Ras-ERK—were also down-regulated in LPS-stimulated TAGLN2-deficient macrophages. Moreover, TAGLN2 −/− mice showed higher mortality after bacterial infection than wild-type littermates. Thus, our results revealed a novel function of TAGLN2 as a molecular armament required for host defense.

Transgelin-2 in immunity: Its implication in cell therapy

“…Each isoform performs unique biological roles and is expressed in different biological conditions. For example, transgelin‐2, the only transgelin protein with an upstream promoter region containing a NF‐κB consensus motif, is largely induced by the NF‐κB pathway in macrophages, while the other two isoforms are not significantly influenced …”

“…The property of transgelin‐2 allowing it to be intercalated into the each G‐actin can also influence the stability of F‐actins . In cells, this property may result in the augmentation of F‐actin contents at the distal‐supramolecular activation cluster (d‐SMAC) of the immunological synapse (IS) in T cells, localization at the filopodia of B cells during B–T conjugation, and ruffles and phagocytic cups in macrophages …”

“…We first provide the biochemical characteristics of transgelin‐2 and its regulation in immune tissues and cells. We then review recently uncovered physiological functions of transgelin‐2 in the immune system; this small ABP regulates cytoskeletal actin dynamics and stabilizes immune synapses that form when antigen‐recognizing T cells meet antigen‐presenting cells (APCs) or macrophages phagocytose infected bacteria . Several studies have suggested the feasibility of transgelin‐2 as an endogenous factor to enhance T cell function, thereby boosting the antitumor response of cytotoxic T cells for immune cell therapy.…”

Actin stabilizer TAGLN2 potentiates adoptive T cell therapy by boosting the inside-out costimulation via lymphocyte function-associated antigen-1

“…From this perspective, we utilized TAGLN2 as we found in a previous report that TAGLN2 increases F-actin contents through stabilization of F-actin in T cells during IS formation. 17 Recently, we also found that TAGLN2 is significantly upregulated in macrophages in response to lipopolysaccharide and enhances macrophage phagocytic function, 26 demonstrating that TAGLN2 plays an essential role in actin dynamics at the immunological or phagocytic synapses. In the present study, more strikingly, drastic down-regulation of TAGLN2 in T cells from severe E0771 tumor-bearing mice further emphasizes that TAGLN2 is an important actin regulator for cytotoxic T cell adhesion to tumor target cells.…”

LRRK2 Kinase Plays an Important Role in the Intracellular Survival of Brucella abortus 2308 in Murine Macrophages and in a Mouse Infection Model

“…Macrophages, the first-line host defense against pathogenic microorganisms, are activated by cytokines (e.g., TNF-α, IFN-γ, and IL-4) and bacterial virulence factors (Mitchell et al, 2016;Salim et al, 2016). Activated macrophages trigger the activation of immunity-related signalling pathways, leading to the elimination of pathogenic bacteria (Kim et al, 2017). Previous studies have shown the clearance of almost 90% of invading Brucella by macrophages, but the remaining 10% can establish a safe niche for growth and reproduction in the endoplasmic reticulum (Von et al, 2012).…”