BACKGROUND: Regenerative medicine and transplantation science continuously seek methods to circumvent immune-mediated rejection and promote tissue regeneration. Sertoli cells, with their inherent immunoprotective properties, emerge as pivotal players in this quest. However, whether Sertoli cells can play immunomodulatory role in tadpole tail regeneration and can thus benefit the regeneration process are needed to be discovered. METHODS: Immature Sertoli cells from Xenopus tropicalis (XtiSCs) were transplanted into X. tropicalis tadpoles, followed by the amputation of the final third of their tails. We assessed the migration of XtiSCs, tail regeneration length, muscle degradation and growth, and macrophage counts across various regions including the entire tail, tail trunk, injection site, and regeneration site. The interactions between XtiSCs and macrophages were examined using a confocal microscope. To deplete macrophages, clodronate liposomes were administered prior to the transplantation of XtiSCs, while the administration of control liposomes acted as a negative control. Student's t-test was used to compare the effects of XtiSCs injection to those of a 2/3PBS injection across groups with no liposomes, control liposomes, and clodronate liposomes. RESULTS: XtiSCs have excellent viability after transplantation to tadpole tail and remarkable homing capabilities to the regeneration site after tail amputation. XtiSCs injection increased macrophage numbers at 3 days post-amputation and 5 days post-amputation in the tail trunk, specifically at the injection site and at the regenerated tail, in a macrophage depleted environment (clodronate-liposome injection). What's more, XtiSCs injection decreased muscle fibers degradation significantly at 1 day post-amputation and facilitated new muscle growth significantly at 3 days post-amputation. In addition, whole-mount immunostaining showed that some XtiSCs co-localized with macrophages. And we observed potential mitochondria transport from XtiSCs to macrophages using MitoTracker staining in tadpole tail. CONCLUSIONS: Our study delineates the novel role of XtiSCs in facilitating muscle regeneration post tadpole tail amputation, underscoring a unique interaction with macrophages that is crucial for regenerative success. This study not only highlights the therapeutic potential of Sertoli cells in regenerative medicine but also opens avenues for clinical translation, offering insights into immunoregulatory strategies that could enhance tissue regeneration and transplant acceptance.

• Klíčová slova
• Xenopus, Immature sertoli cells, Macrophages, Regeneration, Tadpole,
• MeSH
• imunomodulace MeSH
• larva * MeSH
• makrofágy * metabolismus   imunologie   MeSH
• ocas MeSH
• regenerace * MeSH
• Sertoliho buňky * cytologie   metabolismus   MeSH
• Xenopus * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Macrophages represent heterogeneous cell population with important roles in defence mechanisms and in homoeostasis. Tissue macrophages from diverse anatomical locations adopt distinct activation states. M1 and M2 macrophages are two polarized forms of mononuclear phagocyte in vitro differentiation with distinct phenotypic patterns and functional properties, but in vivo, there is a wide range of different macrophage phenotypes in between depending on the microenvironment and natural signals they receive. In human infections, pathogens use different strategies to combat macrophages and these strategies include shaping the macrophage polarization towards one or another phenotype. Macrophages infiltrating the tumours can affect the patient's prognosis. M2 macrophages have been shown to promote tumour growth, while M1 macrophages provide both tumour-promoting and anti-tumour properties. In autoimmune diseases, both prolonged M1 activation, as well as altered M2 function can contribute to their onset and activity. In human atherosclerotic lesions, macrophages expressing both M1 and M2 profiles have been detected as one of the potential factors affecting occurrence of cardiovascular diseases. In allergic inflammation, T2 cytokines drive macrophage polarization towards M2 profiles, which promote airway inflammation and remodelling. M1 macrophages in transplantations seem to contribute to acute rejection, while M2 macrophages promote the fibrosis of the graft. The view of pro-inflammatory M1 macrophages and M2 macrophages suppressing inflammation seems to be an oversimplification because these cells exploit very high level of plasticity and represent a large scale of different immunophenotypes with overlapping properties. In this respect, it would be more precise to describe macrophages as M1-like and M2-like.

• Klíčová slova
• M1/M2, cancer, differentiation, infection, macrophages, polarisation,
• MeSH
• buněčná diferenciace MeSH
• cytokiny * MeSH
• fenotyp MeSH
• lidé MeSH
• makrofágy * MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny * MeSH

Macrophages are a specific group of cells found in all body tissues. They have specific characteristics in each of the tissues that correspond to the functional needs of the specific environment. These cells are involved in a wide range of processes, both pro-inflammatory and anti-inflammatory ("wound healing"). This is due to their specific capacity for so-called polarization, a phenotypic change that is, moreover, partially reversible compared to other differentiated cells of the human body. This promises a wide range of possibilities for its influence and thus therapeutic use. In this article, we therefore review the mechanisms that cause polarization, the basic classification of polarized macrophages, their characteristic markers and the effects that accompany these phenotypic changes. Since the study of pulmonary (and among them mainly alveolar) macrophages is currently the focus of scientific interest of many researchers and these macrophages are found in very specific environments, given mainly by the extremely high partial pressure of oxygen compared to other locations, which specifically affects their behavior, we will focus our review on this group.

• MeSH
• antiflogistika * farmakologie   MeSH
• buněčná diferenciace fyziologie   MeSH
• lidé MeSH
• makrofágy * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antiflogistika * MeSH

In recent years, there has been an increasing incidence of metabolic syndrome, type 2 diabetes, and cardiovascular events related to insulin resistance. As one of the target organs for insulin, adipose tissue is essential for maintaining in vivo immune homeostasis and metabolic regulation. Currently, the specific adipose tissue mechanisms involved in insulin resistance remain incompletely understood. There is increasing evidence that the process of insulin resistance is mostly accompanied by a dramatic increase in the number and phenotypic changes of adipose tissue macrophages (ATMs). In this review, we discuss the origins and functions of ATMs, some regulatory factors of ATM phenotypes, and the mechanisms through which ATMs mediate insulin resistance. We explore how ATM phenotypes contribute to insulin resistance in adipose tissue. We expect that modulation of ATM phenotypes will provide a novel strategy for the treatment of diseases associated with insulin resistance.

• MeSH
• diabetes mellitus 2. typu * metabolismus   MeSH
• inzulinová rezistence * fyziologie   MeSH
• lidé MeSH
• makrofágy metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• zánět metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PURPOSE: About 15% of patients with common variable immunodeficiency (CVID) develop a small intestinal enteropathy, which resembles celiac disease with regard to histopathology but evolves from a distinct, poorly defined pathogenesis that has been linked in some cases to chronic norovirus (NV) infection. Interferon-driven inflammation is a prominent feature of CVID enteropathy, but it remains unknown how NV infection may contribute. METHODS: Duodenal biopsies of CVID patients, stratified according to the presence of villous atrophy (VA), IgA plasma cells (PCs), and chronic NV infection, were investigated by flow cytometry, multi-epitope-ligand cartography, bulk RNA-sequencing, and RT-qPCR of genes of interest. RESULTS: VA development was connected to the lack of intestinal (IgA+) PC, a T helper 1/T helper 17 cell imbalance, and increased recruitment of granzyme+CD8+ T cells and pro-inflammatory macrophages to the affected site. A mixed interferon type I/III and II signature occurred already in the absence of histopathological changes and increased with the severity of the disease and in the absence of (IgA+) PCs. Chronic NV infection exacerbated this signature when compared to stage-matched NV-negative samples. CONCLUSIONS: Our study suggests that increased IFN signaling and T-cell cytotoxicity are present already in mild and are aggravated in severe stages (VA) of CVID enteropathy. NV infection preempts local high IFN-driven inflammation, usually only seen in VA, at milder disease stages. Thus, revealing the impact of different drivers of the pathological mixed IFN type I/III and II signature may allow for more targeted treatment strategies in CVID enteropathy and supports the goal of viral elimination.

• Klíčová slova
• CVID, Cytotoxic T cell response, Duodenum, Interferon response genes, Norovirus, Villous atrophy,
• MeSH
• atrofie komplikace   patologie   MeSH
• běžná variabilní imunodeficience * komplikace   imunologie   MeSH
• CD8-pozitivní T-lymfocyty MeSH
• imunoglobulin A MeSH
• infekce viry z čeledi Caliciviridae * imunologie   MeSH
• interferony MeSH
• lidé MeSH
• Norovirus * fyziologie   MeSH
• zánět komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• imunoglobulin A MeSH
• interferony MeSH

Toxoplasma gondii Nicolle et Manceaux, 1909, the etiologic agent of toxoplasmosis, was considered a clonal population with three distinct genetic lineages (I, II and III); however, sequence analysis of different strains has revealed distinct atypical genotypes. Macrophages are essential for immunity against toxoplasmosis and differential cell regulation may affect the course of the disease. In this context, our study aims to investigate the infection by TgChBrUD2, a highly virulent atypical Brazilian strain of T. gondii, on the activation and polarisation of human macrophages. Human macrophage-like cells obtained from THP-1 cells were infected with TgChBrUD2, RH or ME49 strains of T. gondii to evaluate the impact of parasite infection on macrophage polarisation. Our results indicate that the TgChBrUD2 and ME49 strains of T. gondii induced a classic activation of human macrophages, which was confirmed by the high rate of spindle-shaped macrophages, low amount of urea and increase in the levels of nitrite, as well as the down-regulation of M2-markers. In contrast, RH strain promoted an alternative activation of macrophages. The polarisation of human macrophages towards an M1 subtype mediated by TgChBrUD2 and ME49 strains resulted in a low parasite burden, with high levels of IL-6 and MIF. Finally, the M2 subtype triggered by the RH strain culminated in a lower intracellular proliferation index. We concluded that the atypical (TgChBrUD2) and clonal (ME49) strains are able to elicit an M1 subtype, which results in parasitism control, partially explained by the high levels of IL-6 and MIF produced during the infection by these genotypes. In contrast, the clonal (RH) strain promoted a macrophage polarisation towards an M2 subtype, marked by a high parasite burden, with a weak modulation of pro-inflammatory cytokines. Thus, atypical strains can present different mechanisms of pathogenicity and transmissibility compared to clonal strains, as well as they can use distinct strategies to evade the host's immune response and ensure their survival.

• Klíčová slova
• TgChBrUD2 strain, clonal strains, macrophage polarisation, toxoplasmosis,
• MeSH
• cytokiny MeSH
• dusitany MeSH
• interleukin-6 MeSH
• lidé MeSH
• makrofágy parazitologie   MeSH
• močovina MeSH
• paraziti * MeSH
• Toxoplasma * MeSH
• toxoplazmóza * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Brazílie epidemiologie   MeSH
• Názvy látek
• cytokiny MeSH
• dusitany MeSH
• interleukin-6 MeSH
• močovina MeSH

Head and neck squamous cell carcinomas (HNSCC) can be induced by smoking or alcohol consumption, but a growing part of cases relate to a persistent high-risk papillomavirus (HPV) infection. Viral etiology has a beneficial impact on the prognosis, which may be explained by a specific immune response. Tumor associated macrophages (TAMs) represent the main immune population of the tumor microenvironment with a controversial influence on the prognosis. In this study, the level, phenotype, and spatial distribution of TAMs were evaluated, and the expression of TAM-associated markers was compared in HPV positive (HPV+) and HPV negative (HPV-) tumors. Seventy-three formalin and embedded in paraffin (FFPE) tumor specimens were examined using multispectral immunohistochemistry for the detection of TAM subpopulations in the tumor parenchyma and stroma. Moreover, the mRNA expression of TAM markers was evaluated using RT-qPCR. Results were compared with respect to tumor etiology, and the prognostic significance was evaluated. In HPV- tumors, we observed more pro-tumorigenic M2 in the stroma and a non-macrophage arginase 1 (ARG1)-expressing population in both compartments. Moreover, higher mRNA expression of M2 markers-cluster of differentiation 163 (CD163), ARG1, and prostaglandin-endoperoxide synthase 2 (PTGS2)-was detected in HPV- patients, and of M1 marker nitric oxide synthase 2 (NOS2) in HPV+ group. The expression of ARG1 mRNA was revealed as a negative prognostic factor for overall survival of HNSCC patients.

• Klíčová slova
• HPV, arginase 1, head and neck carcinoma, macrophages, prognosis,
• Publikační typ
• časopisecké články MeSH

Non-infectious uveitis is considered an autoimmune disease responsible for a significant burden of blindness in developed countries and recent studies have linked its pathogenesis to dysregulation of the gut microbiota. We tested the immunomodulatory properties of two probiotics, Escherichia coli Nissle 1917 (EcN) and E. coli O83:K24:H31 (EcO), in a model of experimental autoimmune uveitis (EAU). To determine the importance of bacterial viability and treatment timing, mice were orally treated with live or autoclaved bacteria in both preventive and therapeutic schedules. Disease severity was assessed by ophthalmoscopy and histology, immune phenotypes in mesenteric and cervical lymph nodes were analyzed by flow cytometry and the gut immune environment was analyzed by RT-PCR and/or gut tissue culture. EcN, but not EcO, protected against EAU but only as a live organism and only when administered before or at the time of disease induction. Successful prevention of EAU was accompanied by a decrease in IRBP-specific T cell response in the lymph nodes draining the site of immunization as early as 7 days after the immunization and eye-draining cervical lymph nodes when the eye inflammation became apparent. Furthermore, EcN promoted an anti-inflammatory response in Peyer's patches, increased gut antimicrobial peptide expression and decreased production of inducible nitric oxide synthase in macrophages. In summary, we show here that EcN controls inflammation in EAU and suggest that probiotics may have a role in regulating the gut-eye axis.

• Klíčová slova
• Escherichia coli Nissle 1917, experimental autoimmune uveitis, macrophages, mucosal immune system, probiotics,
• MeSH
• autoimunitní nemoci terapie   MeSH
• Escherichia coli * MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• probiotika * aplikace a dávkování   farmakologie   MeSH
• střevní sliznice patologie   MeSH
• uveitida terapie   MeSH
• zánět terapie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chronic inflammation with a wide spectrum of connected diseases (e [...].

• MeSH
• fytonutrienty farmakologie   terapeutické užití   MeSH
• lidé MeSH
• objevování léků MeSH
• regulace genové exprese účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• tradiční čínská medicína MeSH
• zánět farmakoterapie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• úvodní články MeSH
• úvodníky MeSH
• Názvy látek
• fytonutrienty MeSH

The adverse immune responses to implantable biomedical devices is a general problem with important consequences for the functionality of implants. Immunomodulatory soft hydrogel-based interfaces between the implant and the host can attenuate these reactions. Moreover, encapsulation of the patient's own immune cells into these interfaces can lead to the personalisation of implants from the immune reaction point of view. Herein, we described a co-crosslinkable composite hydrogel (composed of gelatin and hyaluronic acid), which could be used for the encapsulation of macrophages in the presence of an anti-inflammatory phenotype-fixing cytokine cocktail. To mimick the incoming immune cells on the coating surface in vivo, peripheral blood mononuclear cells were seeded on the hydrogels. The encapsulation of monocytic cells into the composite hydrogels in the presence of cytokine cocktails at 5× or 10× concentrations led to the spreading of the encapsulated cells instead of the formation of clusters. Moreover, the secretion of the anti-inflammatory cytokines IL-1RA and CCL-18 was significantly increased. The attachment of PBMC to the surface of the hydrogel is dependent on the hydrogel composition and also significantly increased in the presence of the cytokine cocktail together with the number of CD68+ cells on the hydrogel surface. Our study demonstrates that the delivery of a polarisation cocktail with biocompatible hydrogels can control the initial response by the incoming immune cells. This effect can be improved by the encapsulation of autologous monocytes that are also polarised by the cytokine cocktail and secrete additional anti-inflammatory cytokines. This interface can fine tune the initial immune response to an implanted biomaterial in a personalised manner.

• Publikační typ
• časopisecké články MeSH