scholarly journals Translation of Collagen Ultrastructure to Biomaterial Fabrication for Material Independent but Highly Efficient Topographic Immunomodulation

2021 ◽  
Author(s):  
matthias ryma ◽  
tina tylek ◽  
julia liebscher ◽  
robin fernandez ◽  
christoph böhm ◽  
...  
Keyword(s):  
Immune Cells ◽  
Macrophage Polarization ◽  
Healing Process ◽  
Human Monocyte ◽  
Collagen Fibers ◽  
Collagen I ◽  
Human Macrophage ◽  
Type I ◽  
Native Collagen ◽  
Surface Patterns

<div>Supplement-free induction of cellular differentiation and polarization solely through the topography of materials is an auspicious strategy but has so far significantly lacked behind the efficiency and intensity of media-supplementation based protocols. For immune cells, low intensity effects were achieved on rhodent cells using standard technologically driven surface patterns and scaffold geometries, but no effects could be achieved for human immune cells. <br></div><p> </p> <p>Consistent with the idea that 3D structural motives in the extracellular matrix possess immunomodulatory capacity as part of the natural healing process, we found that human monocyte-derived macrophages show a strong M2a like pro-healing polarization when cultured on type I rat-tail collagen fibers (hereafter termed "collagen I") but not on collagen I films. <br></p><p>Therefore, we hypothesized that highly aligned nanofibrils also of synthetic polymers, if packed into larger bundles in 3D topographical similarity to native collagen I, would induce a localized macrophage polarization. <br></p> <p> </p> <p>For the automated fabrication of such bundles in a 3D printing manner, we pioneered the strategy of "Melt Electrofibrillation" by the integration of flow directed polymer phase separation into Melt Electrowriting and subsequent selective dissolution of the matrix polymer. This process yields nano-fiber bundles with a remarkable structural similarity to native collagen I fibers, particularly for medical grade polycaprolactone (PCL). </p> <p> </p> <p>These biomimetic fibrillar structures indeed induced a pronounced elongation of human monocyte-derived macrophages and unprecedentedly triggered their M2-like polarization as efficiently as IL-4 cytokine treatment.</p> <p> </p> <p>Our data evidence the biological importance of human macrophage-elongation on collagen fibers and pioneers a strategy to fabricate scaffolds that exploit this effect to drive macrophage polarization through precise and biomimetic material design. </p>

scholarly journals Translation of Collagen Ultrastructure to Biomaterial Fabrication for Material Independent but Highly Efficient Topographic Immunomodulation

2021 ◽  
Author(s):  
matthias ryma ◽  
tina tylek ◽  
julia liebscher ◽  
robin fernandez ◽  
christoph böhm ◽  
...  
Keyword(s):  
Immune Cells ◽  
Macrophage Polarization ◽  
Healing Process ◽  
Human Monocyte ◽  
Collagen Fibers ◽  
Collagen I ◽  
Human Macrophage ◽  
Type I ◽  
Native Collagen ◽  
Surface Patterns

<div>Supplement-free induction of cellular differentiation and polarization solely through the topography of materials is an auspicious strategy but has so far significantly lacked behind the efficiency and intensity of media-supplementation based protocols. For immune cells, low intensity effects were achieved on rhodent cells using standard technologically driven surface patterns and scaffold geometries, but no effects could be achieved for human immune cells. <br></div><p> </p> <p>Consistent with the idea that 3D structural motives in the extracellular matrix possess immunomodulatory capacity as part of the natural healing process, we found that human monocyte-derived macrophages show a strong M2a like pro-healing polarization when cultured on type I rat-tail collagen fibers (hereafter termed "collagen I") but not on collagen I films. <br></p><p>Therefore, we hypothesized that highly aligned nanofibrils also of synthetic polymers, if packed into larger bundles in 3D topographical similarity to native collagen I, would induce a localized macrophage polarization. <br></p> <p> </p> <p>For the automated fabrication of such bundles in a 3D printing manner, we pioneered the strategy of "Melt Electrofibrillation" by the integration of flow directed polymer phase separation into Melt Electrowriting and subsequent selective dissolution of the matrix polymer. This process yields nano-fiber bundles with a remarkable structural similarity to native collagen I fibers, particularly for medical grade polycaprolactone (PCL). </p> <p> </p> <p>These biomimetic fibrillar structures indeed induced a pronounced elongation of human monocyte-derived macrophages and unprecedentedly triggered their M2-like polarization as efficiently as IL-4 cytokine treatment.</p> <p> </p> <p>Our data evidence the biological importance of human macrophage-elongation on collagen fibers and pioneers a strategy to fabricate scaffolds that exploit this effect to drive macrophage polarization through precise and biomimetic material design. </p>

Pathomechanics of Hallux Valgus: Biomechanical and Immunohistochemical Study

2005 ◽  
Vol 26 (9) ◽  
pp. 732-738 ◽  
Author(s):  
Eiichi Uchiyama ◽  
Harold B. Kitaoka ◽  
Zong-Ping Luo ◽  
Joseph P. Grande ◽  
Hideji Kura ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Hallux Valgus ◽  
Tensile Modulus ◽  
Metatarsophalangeal Joint ◽  
Collagen Fibers ◽  
Collagen I ◽  
Type Iii Collagen ◽  
Type I ◽  
First Metatarsophalangeal Joint ◽  
Collagen Iii

Background: One factor believed to contribute to the development of hallux valgus is an abnormality in collagen structure and makeup of the medial collateral ligament (MCL) of the first metatarsophalangeal joint (MTPJ). We hypothesized that the mechanical properties of the MCL in feet with hallux valgus are significantly different from those in normal feet and that these differences may be related to alterations in the type or distribution of collagen fibers at the interface between the MCL and the bone. Materials and Methods: Seven normal fresh-frozen cadaver feet were compared to four cadaver feet that had hallux valgus deformities. The MCL mechanical properties, structure of collagen fibers, and content proportion of type I and type III collagen were determined. Results: The load-deformation and stress-strain curves were curvilinear with three regions: laxity, toe, and linear regions. Laxity of the MCL in feet with hallux valgus was significantly larger than that of normal feet ( p = 0.022). Stiffness and tensile modulus in the toe region in feet with hallux valgus were significantly smaller than those in normal feet ( p = 0.004); however, stiffness and tensile modulus in the linear region were not significantly different. The MCL collagen fibrils in the feet with hallux valgus had a more wavy distribution than the fibrils in the normal feet. Conclusions: In general, strong staining for collagen III and to a lesser extent, collagen I was observed at the interface between the MCL and bone in the feet with hallux valgus but not in the normal feet. These results indicate that the abnormal mechanical properties of the MCL in feet with hallux valgus may be related to differences in the organization of collagen I and collagen III fibrils.

scholarly journals A primary human macrophage-enteroid co-culture model to investigate mucosal gut physiology and host-pathogen interactions

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Gaelle Noel ◽  
Nicholas W. Baetz ◽  
Janet F. Staab ◽  
Mark Donowitz ◽  
Olga Kovbasnjuk ◽  
...  
Keyword(s):  
Intestinal Epithelium ◽  
Immune Cells ◽  
Barrier Function ◽  
Morphological Changes ◽  
Human Monocyte ◽  
Human Macrophage ◽  
Primary Human Macrophage ◽  
Cell Height ◽  
Culture Model ◽  
Gut Physiology

Abstract Integration of the intestinal epithelium and the mucosal immune system is critical for gut homeostasis. The intestinal epithelium is a functional barrier that secludes luminal content, senses changes in the gut microenvironment, and releases immune regulators that signal underlying immune cells. However, interactions between epithelial and innate immune cells to maintain barrier integrity and prevent infection are complex and poorly understood. We developed and characterized a primary human macrophage-enteroid co-culture model for in-depth studies of epithelial and macrophage interactions. Human intestinal stem cell-derived enteroid monolayers co-cultured with human monocyte-derived macrophages were used to evaluate barrier function, cytokine secretion, and protein expression under basal conditions and following bacterial infection. Macrophages enhanced barrier function and maturity of enteroid monolayers as indicated by increased transepithelial electrical resistance and cell height. Communication between the epithelium and macrophages was demonstrated through morphological changes and cytokine production. Intraepithelial macrophage projections, efficient phagocytosis, and stabilized enteroid barrier function revealed a coordinated response to enterotoxigenic and enteropathogenic E. coli infections. In summary, we have established the first primary human macrophage-enteroid co-culture system, defined conditions that allow for a practical and reproducible culture model, and demonstrated its suitability to study gut physiology and host responses to enteric pathogens.

scholarly journals Defining the Immune Responses for SARS-CoV-2-Human Macrophage Interactions

2021 ◽  
Author(s):  
Mai Mostafa ◽  
Pravin Yeapuri ◽  
Jatin Machhi ◽  
Katherine Olson ◽  
Farah Shahjin ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Innate Immune Response ◽  
Human Monocyte ◽  
Innate Immune ◽  
Mononuclear Phagocytes ◽  
Human Macrophage ◽  
Type I ◽  
Innate Immune Signaling ◽  
Organ Tissue

Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end organ malfunctions. All follow an abortive viral infection. To elucidate SARS-CoV-2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the SARS-CoV-2 receptor, the angiotensin-converting enzyme 2, paralleled monocyte-macrophage differentiation it failed to affect productive viral infection. In contrast, simple macrophage viral exposure led to robust pro-inflammatory cytokine and chemokine expression but attenuated type I interferon (IFN) activity. Both paralleled dysregulation of innate immune signaling pathways specifically those linked to IFN. We conclude that the SARS-CoV-2-infected host mounts a robust innate immune response characterized by a pro-inflammatory storm heralding consequent end-organ tissue damage.

scholarly journals In vivo single cell transcriptomics reveals Klebsiella pneumoniae rewiring of lung macrophages to promote infection

2021 ◽  
Author(s):  
Amy Dumigan ◽  
Oisin Cappa ◽  
Brenda Morris ◽  
Joana sa-Pessoa Graca Santos ◽  
Ricardo Calderon-Gonzalez ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Single Cell ◽  
Macrophage Polarization ◽  
Resistant Bacteria ◽  
Human Macrophage ◽  
Type I ◽  
Dependent Manner ◽  
Type I Ifn ◽  
Lung Macrophages

The strategies deployed by antibiotic resistant bacteria to counteract host defences are poorly understood. Here, we elucidate a novel host-pathogen interaction that results in the control of lung macrophage polarisation by the human pathogen Klebsiella pneumoniae. We identify interstitial macrophages (IMs) as the main population of lung macrophages associated with Klebsiella. Single cell transcriptomics and trajectory analysis of cells uncover that type I IFN and IL10 signalling, and macrophage polarization are characteristic of infected IMs, whereas Toll-like receptor (TLR) and Nod-like receptor signalling are features of infected alveolar macrophages. Klebsiella-induced macrophage polarization is a singular M2-type we termed M(Kp). To rewire macrophages towards M(Kp), K. pneumoniae hijacks a hitherto unknown TLR-type I IFN-IL10-STAT6 innate axis. Absence of STAT6 limits the intracellular survival of Klebsiella whereas the inhibition of STAT6 facilitates the clearance of the pathogen in vivo. Glycolysis characterises M(Kp) metabolism, and inhibition of glycolysis results in clearance of intracellular Klebsiella. We demonstrate the capsule polysaccharide is the Klebsiella factor governing M(Kp). Klebsiella also skews human macrophage polarization towards M(Kp) in a type I IFN-IL10-STAT6-dependent manner. Altogether, our work demonstrates that Klebsiella induction of M(Kp) represents a hitherto unknown strategy to overcome host restriction during pneumonia.

scholarly journals Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions

2021 ◽  
Vol 12 ◽  
Author(s):  
Mai M. Abdelmoaty ◽  
Pravin Yeapuri ◽  
Jatin Machhi ◽  
Katherine E. Olson ◽  
Farah Shahjin ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Human Monocyte ◽  
Innate Immune ◽  
Mononuclear Phagocytes ◽  
Human Macrophage ◽  
Type I ◽  
Innate Immune Signaling ◽  
Life Threatening ◽  
Organ Tissue

Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end-organ malfunctions. All follow the presence of persistent viral components and virions without evidence of viral replication. To elucidate SARS-CoV-2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the SARS-CoV-2 receptor, the angiotensin-converting enzyme 2, paralleled monocyte-macrophage differentiation, it failed to affect productive viral infection. In contrast, simple macrophage viral exposure led to robust pro-inflammatory cytokine and chemokine expression but attenuated type I interferon (IFN) activity. Both paralleled dysregulation of innate immune signaling pathways, specifically those linked to IFN. We conclude that the SARS-CoV-2-infected host mounts a robust innate immune response characterized by a pro-inflammatory storm heralding end-organ tissue damage.

scholarly journals Effect of stimulation time on the expression of human macrophage polarization markers

2021 ◽  
Author(s):  
Duygu Unuvar Purcu ◽  
Asli Korkmaz ◽  
Sinem Gunalp ◽  
Derya Goksu Helvaci ◽  
Yonca Erdal ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
False Negative ◽  
Human Monocyte ◽  
Human Macrophage ◽  
Environmental Signals ◽  
Reference Guide ◽  
Protein Levels ◽  
Negative Results

Macrophages are highly plastic cells that can polarize into functionally distinct subsets in vivo and in vitro in response to environmental signals. The development of protocols to model macrophage polarization in vitro greatly contributes to our understanding of macrophage biology. Macrophages are divided into two main groups: Pro-inflammatory M1 macrophages (classically activated) and anti-inflammatory M2 macrophages (alternatively activated), based on several key surface markers and the production of inflammatory mediators. However, the expression of these common macrophage polarization markers is greatly affected by the stimulation time used. Unfortunately, there is no consensus yet regarding the optimal stimulation times for particular macrophage polarization markers in in vitro experiments. This situation is problematic, (i) as analysing a particular marker at a suboptimal time point can lead to false-negative results, and (ii) as it clearly impedes the comparison of different studies. Using human monocyte-derived macrophages (MDMs) in vitro, we analysed how the expression of the main polarization markers for M1 (CD64, CD86, CXCL9, CXCL10, HLA-DR, IDO1, IL1b, IL12p70, TNF), M2a (CD200R, CD206, CCL17, CCL22, IL-10, TGM2), and M2c (CD163, IL-10, TGFb) macrophages changes over time at mRNA and protein levels. Our data establish the most appropriate stimulation time for the analysis of the expression of human macrophage polarization markers in vitro. Providing such a reference guide will likely facilitate the investigation of macrophage polarization and its reproducibility.

scholarly journals LXR nuclear receptors prompt a pro-inflammatory gene and functional profile in human macrophages

2021 ◽  
Author(s):  
Arturo González de la Aleja1 ◽  
Mónica Torres-Torresano ◽  
Juan Vladimir de la Rosa ◽  
Barbara Alonso ◽  
Enrique Capa-Sardón ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Cholesterol Metabolism ◽  
Macrophage Polarization ◽  
Human Monocyte ◽  
Gene Signature ◽  
Human Macrophage ◽  
Human Macrophages ◽  
Inflammatory Gene ◽  
Anti Inflammatory

Abstract Liver X Receptors (LXR) control cholesterol metabolism and exert anti-inflammatory actions in activated macrophages. However, their contribution to human macrophage polarization in the absence of pathogenic stimuli remains unclear. In fact, the LXR pathway has been reported to be significantly enriched in pro-inflammatory synovial macrophages from rheumatoid arthritis patients as well as in immunosuppressive tumors-associated macrophages from human metastatic colon tumors. To determine the role of LXR on macrophage differentiation and polarization, we have analyzed the contribution of LXR to the acquisition of the inflammatory and T-cell-activating functions of human monocyte-derived macrophages. We now report that LXR activation prompts the acquisition of a pro-inflammatory gene signature in human macrophages, whereas LXR inactivation results in enrichment of an anti-inflammatory gene profile. Accordingly, activation and inhibition of LXR oppositely alter the production of cytokines (e.g., TNF, IL1b, CCL17, CCL19, IFNb1) and T cell stimulation activities associated to human macrophage polarization. Mechanistically, the LXR-stimulated macrophage polarization shift relies on their ability to modulate the expression of MAFB and MAF, which govern the acquisition of the macrophage anti-inflammatory profile. The pathological significance of the LXR-mediated macrophage polarization shift was demonstrated by the ability of LXR agonists to modulate macrophage polarization promoted by either tumor-derived ascitic fluids or by synovial fluid from rheumatoid arthritis patients. As a whole, our results demonstrate that LXR activation prompts the acquisition of a pro-inflammatory transcriptional and functional specialization in human macrophages .

scholarly journals Early Leukocyte Responses in Ex-Vivo Models of Healing and Non-Healing Human Leishmania (Viannia) panamensis Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Maria Adelaida Gomez ◽  
Ashton Trey Belew ◽  
Adriana Navas ◽  
Mariana Rosales-Chilama ◽  
Julieth Murillo ◽  
...  
Keyword(s):  
Host Cell ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Current Knowledge ◽  
Human Macrophage ◽  
Type I ◽  
Self Healing ◽  
Cell Functions ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Early host-pathogen interactions drive the host response and shape the outcome of natural infections caused by intracellular microorganisms. These interactions involve a number of immune and non-immune cells and tissues, along with an assortment of host and pathogen-derived molecules. Our current knowledge has been predominantly derived from research on the relationships between the pathogens and the invaded host cell(s), limiting our understanding of how microbes elicit and modulate immunological responses at the organismal level. In this study, we explored the early host determinants of healing and non-healing responses in human cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) panamensis. We performed a comparative transcriptomic profiling of peripheral blood mononuclear cells from healthy donors (PBMCs, n=3) exposed to promastigotes isolated from patients with chronic (CHR, n=3) or self-healing (SH, n=3) CL, and compared these to human macrophage responses. Transcriptomes of L. V. panamensis-infected PBMCs showed enrichment of functional gene categories derived from innate as well as adaptive immune cells signatures, demonstrating that Leishmania modulates adaptive immune cell functions as early as after 24h post interaction with PBMCs from previously unexposed healthy individuals. Among differentially expressed PBMC genes, four broad categories were commonly modulated by SH and CHR strains: cell cycle/proliferation/differentiation, metabolism of macromolecules, immune signaling and vesicle trafficking/transport; the first two were predominantly downregulated, and the latter upregulated in SH and CHR as compared to uninfected samples. Type I IFN signaling genes were uniquely up-regulated in PBMCs infected with CHR strains, while genes involved in the immunological synapse were uniquely downregulated in SH infections. Similarly, pro-inflammatory response genes were upregulated in isolated macrophages infected with CHR strains. Our data demonstrate that early responses during Leishmania infection extend beyond innate cell and/or phagocytic host cell functions, opening new frontiers in our understanding of the triggers and drivers of human CL.

scholarly journals Macrophage immunomodulation: An indispensable tool to evaluate the performance of wound dressing biomaterials

2019 ◽  
Vol 17 (1) ◽  
pp. 228080001983035 ◽  
Author(s):  
Patrícia Varela ◽  
Susanna Sartori ◽  
Richard Viebahn ◽  
Jochen Salber ◽  
Gianluca Ciardelli
Keyword(s):  
Wound Healing ◽  
Immune Cells ◽  
Wound Dressing ◽  
Chronic Wounds ◽  
Macrophage Polarization ◽  
Healing Process ◽  
Wound Dressings ◽  
Wound Healing Process ◽  
Immunomodulatory Effects ◽  
Wide Range

A major burden of the healthcare system resides in providing proper medical treatment for all types of chronic wounds, which are usually treated with dressings to induce a faster regeneration. Hence, to reduce healing time and improve the patient’s quality of life, it is extremely important to select the most appropriate constituent material for a specific wound dressing. A wide range of wound dressings exist but their mechanisms of action are poorly explored, especially concerning the immunomodulatory effects that occur from the interactions between immune cells and the biomaterial. Tissue-resident and monocyte-derived recruited macrophages are key regulators of wound repair. These phagocytic immune cells exert specific functions during the different stages of wound healing. The recognition of the substantial role of macrophages in the outcome of the wound healing process requires specific understanding of the immunomodulatory effects of commercially available or newly developed wound dressings. For a precise intervention, it is necessary to obtain more knowledge on macrophage polarization in different phases of wound healing in the presence of the dressings. The main purpose of this review is to collect clinical cases in which macrophage immunomodulation was taken into consideration as an indicator of the performances of novel or mainstream wound dressing materials, including those provided with antimicrobial properties.

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