scholarly journals Mucosal Macrophage Polarization Role in the Immune Modulation

2020 ◽  
Author(s):  
Tsung-Meng Wu ◽  
Shiu-Nan Chen ◽  
Yu-Sheng Wu
Keyword(s):  
Immune Modulation ◽  
Macrophage Polarization

scholarly journals Extracellular Vesicle Mediated Tumor-Stromal Crosstalk Within an Engineered Lung Cancer Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Kayla F. Goliwas ◽  
Hannah M. Ashraf ◽  
Anthony M. Wood ◽  
Yong Wang ◽  
Kenneth P. Hough ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Immune Modulation ◽  
Lung Tumor ◽  
Macrophage Polarization ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Therapeutic Interventions ◽  
Tumor Models

Tumor-stromal interactions within the tumor microenvironment (TME) influence lung cancer progression and response to therapeutic interventions, yet traditional in vitro studies fail to replicate the complexity of these interactions. Herein, we developed three-dimensional (3D) lung tumor models that mimic the human TME and demonstrate tumor-stromal crosstalk mediated by extracellular vesicles (EVs). EVs released by tumor cells, independent of p53 status, and fibroblasts within the TME mediate immunomodulatory effects; specifically, monocyte/macrophage polarization to a tumor-promoting M2 phenotype within this 3D-TME. Additionally, immune checkpoint inhibition in a 3D model that included T cells showed an inhibition of tumor growth and reduced hypoxia within the TME. Thus, perfused 3D tumor models incorporating diverse cell types provide novel insights into EV-mediated tumor-immune interactions and immune-modulation for existing and emerging cancer therapies.

scholarly journals Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
June Seok Heo ◽  
Youjeong Choi ◽  
Hyun Ok Kim
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Modulation ◽  
Human Peripheral Blood ◽  
Macrophage Polarization ◽  
Treg Cells ◽  
M2 Macrophage ◽  
Activated T Cells ◽  
Paracrine Factors ◽  
Arginase 1

Accumulating evidence has shown that the paracrine factors derived from mesenchymal stem cells (MSCs) are capable of regulating the immune system via interaction with various immune cells. In this study, adipose-derived MSCs (AdMSCs) and human peripheral blood monocytes (PBMCs) were isolated and cultured to examine the effects of MSC-induced macrophages (iMΦ) on inflammation and immune modulation. Indirect coculture with MSCs increased the expression of arginase-1 and mannose receptor (CD206), markers of activated M2 macrophages, in the PBMCs demonstrating that MSC-secreted factors promoted M2-MΦ polarization. Additionally, iMΦ exhibited a similar higher inhibitory effect on the growth of activated T cells compared to that in the other groups (AdMSCs only, AdMSCs plus iMΦ), implying that iMΦ can play a sufficient functional role. Interestingly, the population of FoxP3 Treg cells significantly increased when cocultured with iMΦ, suggesting that iMΦ have an immunomodulatory effect on the Treg cells through the modulation of the FoxP3 expression. Notably, iMΦ expressed high levels of immunosuppressive and anti-inflammatory cytokines, namely IL-10 and TSG-6. Furthermore, we confirmed that the AdMSC-derived exosomes modulated macrophage polarization by upregulating the expression of M2 macrophage markers. Conclusively, our results suggest that iMΦ play a significant role in regulating the immunomodulatory- and inflammatory-mediated responses. Thus, iMΦ may be used as a novel stem cell-based cell-free therapy for the treatment of immune-mediated inflammatory disorders.

scholarly journals Dexamethasone Promotes Aspergillus fumigatus Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2

2021 ◽  
Vol 7 (2) ◽  
pp. 70
Author(s):  
Maureen K. Luvanda ◽  
Wilfried Posch ◽  
Jonathan Vosper ◽  
Viktoria Zaderer ◽  
Asma Noureen ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Immune Modulation ◽  
Fungal Infections ◽  
Macrophage Polarization ◽  
Corticosteroid Treatment ◽  
High Morbidity ◽  
Phenotypic Properties ◽  
Metabolic Switch ◽  
Anti Inflammatory ◽  
The Impact

Since long-term corticosteroid treatment is associated with emerging opportunistic fungal infections causing high morbidity and mortality in immune-suppressed individuals, here we characterized the impact of dexamethasone (Dex) treatment on Aspergillus fumigatus-related immune modulation. We found by high content screening and flow cytometric analyses that during monocyte-to-macrophage differentiation, as little as 0.1 µg/mL Dex resulted in a shift in macrophage polarization from M1 to M2-like macrophages. This macrophage repolarization mediated via Dex was characterized by significant upregulation of the M2 marker CD163 and downmodulation of M1 markers CD40 and CD86 as well as changes in phenotypic properties and adherence. These Dex-mediated phenotypic alterations were furthermore associated with a metabolic switch in macrophages orchestrated via PKM2. Such treated macrophages lost their ability to prevent Aspergillus fumigatus germination, which was correlated with accelerated fungal growth, destruction of macrophages, and induction of an anti-inflammatory cytokine profile. Taken together, repolarization of macrophages following corticosteroid treatment and concomitant switch to an anti-inflammatory phenotype might play a prominent role in triggering invasive aspergillosis (IA) due to suppression of innate immunological responses necessary to combat extensive fungal outgrowth.

scholarly journals Tumor-Derived Extracellular Vesicles: A Means of Co-opting Macrophage Polarization in the Tumor Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Theodore Reed ◽  
Jeffrey Schorey ◽  
Crislyn D’Souza-Schorey
Keyword(s):  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Immune Modulation ◽  
Macrophage Polarization ◽  
Cell Types ◽  
Heterogeneous Population ◽  
Functional Plasticity ◽  
Bioactive Proteins ◽  
Membrane Bound ◽  
Almost All

Extracellular vesicles (EVs) are a heterogeneous population of membrane-bound parcels of bioactive proteins, nucleic acids, and lipids released from almost all cell types. The diversity of cargo packaged into EVs proffer the induction of an array of effects on recipient cells. EVs released from tumor cells have emerged as a vital means of communication and immune modulation within the tumor microenvironment (TME). Macrophages are an important contributor to the TME with seemingly paradoxical roles promoting either pro- or anti-tumoral immune function depending on their activated phenotypes. Here, we discuss the influence of tumor-derived extracellular vesicles on the functional plasticity of macrophages in tumor progression.

scholarly journals Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Brett Z. Fite ◽  
James Wang ◽  
Aris J. Kare ◽  
Asaf Ilovitsh ◽  
Michael Chavez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inflammatory Response ◽  
High Intensity ◽  
Immune Modulation ◽  
Focused Ultrasound ◽  
Macrophage Polarization ◽  
Specific Antigen ◽  
Cell Number ◽  
Innate Immune ◽  
High Intensity Focused Ultrasound

AbstractHigh intensity focused ultrasound (HIFU) rapidly and non-invasively destroys tumor tissue. Here, we sought to assess the immunomodulatory effects of MR-guided HIFU and its combination with the innate immune agonist CpG and checkpoint inhibitor anti-PD-1. Mice with multi-focal breast cancer underwent ablation with a parameter set designed to achieve mechanical disruption with minimal thermal dose or a protocol in which tumor temperature reached 65 °C. Mice received either HIFU alone or were primed with the toll-like receptor 9 agonist CpG and the checkpoint modulator anti-PD-1. Both mechanical HIFU and thermal ablation induced a potent inflammatory response with increased expression of Nlrp3, Jun, Mefv, Il6 and Il1β and alterations in macrophage polarization compared to control. Furthermore, HIFU upregulated multiple innate immune receptors and immune pathways, including Nod1, Nlrp3, Aim2, Ctsb, Tlr1/2/4/7/8/9, Oas2, and RhoA. The inflammatory response was largely sterile and consistent with wound-healing. Priming with CpG attenuated Il6 and Nlrp3 expression, further upregulated expression of Nod2, Oas2, RhoA, Pycard, Tlr1/2 and Il12, and enhanced T-cell number and activation while polarizing macrophages to an anti-tumor phenotype. The tumor-specific antigen, cytokines and cell debris liberated by HIFU enhance response to innate immune agonists.

scholarly journals HLA-DRB1 allelic epitopes that associate with autoimmune disease risk or protection activate reciprocal macrophage polarization

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vincent van Drongelen ◽  
Bruna Miglioranza Scavuzzi ◽  
Sarah Veloso Nogueira ◽  
Frederick W. Miller ◽  
Amr H. Sawalha ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Immune Modulation ◽  
Disease Risk ◽  
Macrophage Polarization ◽  
Specific Antigen ◽  
Human Leukocyte ◽  
Allele Specific ◽  
Anti Inflammatory ◽  
Mechanistic Basis

AbstractAssociations between particular human leukocyte antigen (HLA) alleles and susceptibility to—or protection from—autoimmune diseases have been long observed. Allele-specific antigen presentation (AP) has been widely proposed as a culprit, but it is unclear whether HLA molecules might also have non-AP, disease-modulating effects. Here we demonstrate differential macrophage activation by HLA-DRB1 alleles known to associate with autoimmune disease risk or protection with resultant polarization of pro-inflammatory (“M1”) versus anti-inflammatory (“M2”) macrophages, respectively. RNA-sequencing analyses of in vitro-polarized macrophages in the presence of AP-incompetent short synthetic peptides corresponding to the third allelic hypervariable regions coded by those two HLA-DRB1 alleles showed reciprocal activation of pro- versus anti-inflammatory transcriptomes, with implication of corresponding gene ontologies and upstream regulators. These results identify a previously unrecognized mechanism of differential immune modulation by short HLA-DRB1-coded allelic epitopes independent of AP, and could shed new light on the mechanistic basis of HLA-disease association.

scholarly journals Zoledronate Causes a Systemic Shift of Macrophage Polarization towards M1 In Vivo

2021 ◽  
Vol 22 (3) ◽  
pp. 1323
Author(s):  
Manuel Weber ◽  
Andi Homm ◽  
Stefan Müller ◽  
Silke Frey ◽  
Kerstin Amann ◽  
...  
Keyword(s):  
Immune Modulation ◽  
Macrophage Polarization ◽  
Osteonecrosis Of The Jaw ◽  
Surgical Trauma ◽  
Significant Shift ◽  
Breast Cancer Patients ◽  
M1 Polarization ◽  
Somatic Tissues ◽  
Group 1

Background: Immunomodulatory properties of bisphosphonates (BP) are suggested to contribute to the development of medication-associated osteonecrosis of the jaw (MRONJ). Furthermore, bisphosphonate-derived immune modulation might contribute to the anti-metastatic effect observed in breast cancer patients. Macrophages are potential candidates for the mediation of immunomodulatory effects of bisphosphonates. The study aimed to investigate the influence of bisphosphonates alone and in combination with surgical trauma on systemic macrophage polarization (M1 vs. M2) using an in vivo rat model. Methods: A total of 120 animals were divided into four groups. Groups 2 and 4 were treated with 8 × 40 μg/kg body weight of the BP Zoledronate i.p. (week 0–7). Groups 3 and 4 were exposed to surgical trauma (week 8, tooth extraction + tibia fracture), whereas in Group 1 neither medication nor surgical trauma was applied. After 8, 10, 12 and 16 weeks, skin, lung and spleen were immunohistochemically examined for macrophage polarization via expression analysis of CD68, CD163 and iNOS using a tissue microarray (TMA). Results: A significant shift of macrophage polarization towards M1 was observed in skin, spleen and lung tissue of animals, with and without surgical trauma, treated with BP when compared to those without BP application. Surgical trauma did not cause a significant increase towards M1 polarization. Conclusions: BP application leads to a systemic pro-inflammatory situation in vivo, independent of surgical trauma, as evidenced by the shift in macrophage polarization towards M1 in various somatic tissues. This provides a possible explanation for the clinically observed anti-tumor effect of bisphosphonates and might also contribute to pathogenesis of MRONJ.

scholarly journals Nanoparticle Internalization Promotes the Survival of Primary Macrophages

2021 ◽  
Author(s):  
Bader M. Jarai ◽  
Catherine A. Fromen
Keyword(s):  
Immune Modulation ◽  
Ex Vivo ◽  
Macrophage Polarization ◽  
Peritoneal Macrophages ◽  
Cell Therapies ◽  
Foreign Objects ◽  
Promising Target ◽  
Primary Bone ◽  
Poly Ethylene

ABSTRACTMacrophages, a class of tissue resident innate immune cells, are responsible for sequestering foreign objects through the process of phagocytosis, making them a promising target for immune-modulation via particulate engineering. Here, we report that nanoparticle (NP) dosing and cellular internalization via phagocytosis significantly enhances survival of ex vivo cultures of primary bone marrow-derived, alveolar, and peritoneal macrophages over particle-free controls. The enhanced survival is attributed to suppression of caspase-dependent apoptosis and is linked to phagocytosis and lysosomal signaling, which was also found to occur in vivo. Uniquely, poly(ethylene glycol)-based NP treatment does not alter macrophage polarization or lead to inflammatory effects. The enhanced survival phenomenon is also applicable to NPs of alternative chemistries, indicating the potential universality of this phenomenon with relevant drug delivery particles. These findings provide a framework for extending the lifespan of primary macrophages ex vivo for drug screening, vaccine studies, and cell therapies and has implications for any in vivo particulate immune-engineering applications.

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