Tissue Defense Research Articles

The Mechanism and Function of Glia in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease that primarily affects elderly people. The mechanism on onset and progression of PD is unknown. Currently, there are no effective treatment strategies for PD. PD is thought to be the loss of midbrain dopaminergic neurons, but it has recently been discovered that glia also affects brain tissue homeostasis, defense, and repair in PD. The neurodegenerative process is linked to both losses of glial supportive-defensive functions and toxic gain of glial functions. In this article, we reviewed the roles of microglia, astrocytes, and oligodendrocytes in the development of PD, as well as the potential use of glia-related medications in PD treatment.

General Defense Response under Biotic Stress and Its Genetics at Pepper (Capsicum annuum L.)

Since the beginning of resistance breeding, protection of plants against pathogens has relied on specific resistance genes encoding rapid tissue death. Our work has demonstrated in different host–pathogen relationships that plants can defend themselves against pathogens by cell growth and cell division. We first demonstrated this general defence response (GDR) in plants by identifying the gds gene in pepper. Subsequently, the existence of a genetic system for tissue defence became apparent and we set the goal to analyse it. The gdr 1 + 2 genes, which operate the complete GDR system, protect plant tissues from pathogens in a direcessive homozygous state in both host and non-host relationships. The inheritance pattern of the two genes follows a 12:3:1 cleavage of the dominant epistasis. With the knowledge of the gds and gdr 1 + 2 genes, the role of tissue-preserving (GDR) and tissue-destructive (HR) pathways in disease development and their relationship was determined. The genes encoding the general defence response have a low stimulus threshold and are not tissue-destructive and pathogen-specific. They are able to fulfil the role of the plant immune system by providing a general response to various specific stresses. This broad-spectrum general defence system is the most effective in the plant kingdom.

PROTECTIVE EFFECT OF SELENIUM ON DIABETIC NEPHROPATHY IN WISTAR RATS

The objective of the present paper is to study and evaluate the effect of selenium supplementation on diabetic nephropathy caused by reactive species generated following hyperglycemia. This study conducted on thirty-five male albino Wistar rats divided into five groups : the first group serves as control (C), the second group was treated by intraperitoneal injection of selenium (sodium selenite ) at 1.89 mg/kg / day, regarding the 3rd groups diabetes was induced by intraperitoneal injection of 150 mg/kg of alloxan (single dose) (DM). One of the diabetic groups was treated by intraperitoneal injection of insulin, 3 IU/100 g PC twice a day (DTins). Another diabetic group is treated with 1.89 mg/kg/day of sodium selenite intraperitoneally (DTSe), and this for 21 days (the two groups treated with selenium were previously treated by gavage of 2 mg/kg/day for 10 days by the same trace element). The results showed in untreated diabetic rats, a drop in body weight, and an increase in blood glucose (13.87mmol/L ± 0.62), urea (10.58 mmol/l ± 0.59), creatinine (64 µmol/l ± 1.3), and phosphorus (1.8 mmol/l ± 0.2). A decrease in serum calcium (1.9 mmol/l±0.1), total protein (58g/l ± 5), albumin (32 g/l ± 3), insulin (0.64 µ UI/ml ± 0.06) and enzymatic activity of serum G6PDH (109.8 m UI/10GR ± 3). With a decrease in anti-oxidant defense, which results in a reduced renal tissue content in GSH (55 nmol/mg of proteins ± 2.2) and of GPx (0.198 µmol/mg of P ± 0.007) and catalase (14.64 µmol H2O2/mn/mg of P ± 0.8) activities. Meanwhile an increase activity of GSTs (0.791 nmol/mn/mg of P ± 0.03) and the concentration of TBARS (0.382 nmol/mg of P ± 0.02) were observed. Sodium selenite induced the antioxidant defense of renal tissue, which protected it from the free radical damage that can be caused by the injection of Alloxan.

Aqueous extract of Stevia rebaudiana (Bertoni) Bertoni abrogates death-related signaling pathways via boosting the expression profile of oxidative defense systems.

Indigenous inhabitants of South America and other areas have been using stevia as a traditional medicine for years, but its impact on cell signaling pathways has not been well studied yet. We evaluated the impacts of aqueous extract of Stevia rebaudiana (Bertoni) Bertoni on the expression of the selected genes involved in significant cell death modalities, including p53-DNA damage and the cellular antioxidative defense in pancreatic tissues in STZ-induced diabetic rats and murine pancreatic cell lines. The in vivo study revealed that aqueous extract of Stevia significantly upregulated the expression of GSTM1 and P1 and GPX (4.67, 12.08, and 2.81 fold, respectively; all p<.05) along with significant downregulation of the genes which were upregulated by STZ, including apoptotic genes caspase-3 and -9 (-9.80 and -4.16 fold, p<.05, respectively) and necroptotic genes, RIP1K, 2K, and 3K (-9.48, -2.70, and -12.9 fold, respectively, all p<.05). In vitro studies also revealed comparable results. In conclusion, the observed clinical improvements in diabetic rats are the result of overexpression of major genes of antioxidative defense systems in the course of a significant downregulation of major cell death modalities. PRACTICAL APPLICATIONS: The popularity of noncaloric sweeteners, including stevia, has rocketed in recent years, but the consumption of stevia as traditional medicine has a long history. The findings of the current study provide strong mechanistic lines of evidence supporting the beneficial biological effects of stevia as a noncaloric sweetener in diabetes.

Research Updates: Relationship between Gingival Epithelial Intercellular Junctions and Periodontal Pathogenic Bacteria

Gingival epithelial barrier is the first line of defense of periodontal tissues against the invasion of pathogenic bacteria. The destruction of gingival epithelial barrier is closely related to the development of periodontal disease. Studies have shown that periodontal pathogenic bacteria and their inflammatory microenvironment can inhibit the expression of gingival epithelial junctional proteins via molecular mechanisms such as the downregulation of the expression of grainyhead-like protein family and the upregulation of the methylation level of gene promoter of epithelial connexin, and thus cause damage to the gingival epithelial barrier and the development of periodontitis. We herein reviewed the effects of bacteria and inflammatory factors induced by bacterial infection on gingival epithelial intercellular junctions and related mechanisms, and summarized the research progress on the relationship between gingival epithelial intercellular junctions and periodontal pathogenic bacteria in recent years. Most recent studies were focused on i n vitro cytological experiments and animal models of infections caused by a single kind of bacterium. We have suggested that building gingival epithelial organoid model and combining multi-omics approaches with high resolution three-dimensional electron microscopy are expected to help pinpoint the key microorganisms and their most important virulence factors that trigger periodontal microecologcal imbalance and cause functional damage to the gingival epithelial barrier, to reveal the key molecular mechanisms involved in the maintenance and destruction of gingival epithelial barrier function, and to provide new perspectives on the pathogenesis and the clinical prevention and treatment of periodontitis.

2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis—Parkinson's Disease

2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis—Parkinson's Disease

Differentiated plant defense strategies: Herbivore community dynamics affect plant–herbivore interactions

AbstractPlant–herbivore interactions account for much of the biodiversity observed in an ecosystem. Plants may alter defense expression dependent on the specific herbivore present. Many studies focus on the optimization of these defenses against a single herbivore, but in an ecological context, there may be a myriad of herbivores at any given time. We designed a study to examine defenses employed by swamp white oak (Quercus bicolor) against insects and large mammals. We established six deer exclosures with trees located inside and outside each exclosure. Outside the exclosures, physical constraints only allow deer to feed up to abrowselineon trees, whereas insects can potentially access all portions of the tree. Trees inside exclosures were only accessible to insect herbivores. Furthermore, insecticides were applied to half of the exclosures to create insect‐free (i.e., insecticide applied), deer‐free (i.e., inside exclosures), deer‐only (i.e., outside exclosures with insecticide), and herbivore‐free (i.e., inside exclosures with insecticide) environments. This design allowed us to analyze simultaneous defensive responses of individual trees to mammal and insect herbivores. We predicted that because insects represent a continuous threat, plants should invest in fixed concentrations of defenses (e.g., polyphenols, tannins, and condensed tannins), even when deer are absent. When deer are present, plants should increase investment in defenses in tissues that deer have access to. We found that plant defense strategies varied spatially on individual trees. When only insects were present, nutritional constituents (e.g., nitrogen and non‐structural carbohydrates) did not change but antinutritional constituents increased. Contrastingly, when deer were present, both nutritional and antinutritional constituents decreased. We found a decrease in insect functional group diversity when deer were present. Our findings suggest that plants may partition defense strategies depending on the most prominent herbivore pressure. However, changes in insect functional group diversity may result from either changes in plant defense strategy or intraspecific competition among multiple herbivores. Future studies should investigate patterns of chemical heterogeneity displayed by plants in response to diverse herbivore pressures.

The role of systemic diseases and local conditions as risk factors.

The role of systemic diseases and local conditions as risk factors.

Shaping the Innate Immune Response Through Post-Transcriptional Regulation of Gene Expression Mediated by RNA-Binding Proteins.

Innate immunity is the frontline of defense against infections and tissue damage. It is a fast and semi-specific response involving a myriad of processes essential for protecting the organism. These reactions promote the clearance of danger by activating, among others, an inflammatory response, the complement cascade and by recruiting the adaptive immunity. Any disequilibrium in this functional balance can lead to either inflammation-mediated tissue damage or defense inefficiency. A dynamic and coordinated gene expression program lies at the heart of the innate immune response. This expression program varies depending on the cell-type and the specific danger signal encountered by the cell and involves multiple layers of regulation. While these are achieved mainly via transcriptional control of gene expression, numerous post-transcriptional regulatory pathways involving RNA-binding proteins (RBPs) and other effectors play a critical role in its fine-tuning. Alternative splicing, translational control and mRNA stability have been shown to be tightly regulated during the innate immune response and participate in modulating gene expression in a global or gene specific manner. More recently, microRNAs assisting RBPs and post-transcriptional modification of RNA bases are also emerging as essential players of the innate immune process. In this review, we highlight the numerous roles played by specific RNA-binding effectors in mediating post-transcriptional control of gene expression to shape innate immunity.

Scale-dependent trends in the investment of leaf domatia

Abstract Theory predicts that plants invest in defences proportional to the value or amount of tissue at risk. Domatia-bearing plants house predatory arthropods that defend against insect and fungal attack. Though leaf domatia represent a direct investment in the defence of leaf tissues, it remains unknown whether domatia production scales with amount of tissue at risk. I investigated how domatia investment scales with leaf size in 20 species of trees and shrubs from the south-west Pacific. Large-leaved species produced more domatia than smaller leaved species. However, domatia production did not consistently scale with leaf area among individuals of the same species, illustrating that trends in domatia investment are scale-dependent. Overall results suggest the processes modulating the allocation of resources to defence at the interspecific level are distinct from those operating at the intraspecific level.

Toward a Paradigm to Distinguish Distinct Functions of FOXP3+ Regulatory T Cells.

FOXP3+ regulatory T (Treg) cells are a unique subset of CD4+ T cells that classically function as master regulators of immune homeostasis. Besides this canonical suppressive role, which is required to maintain self-tolerance, a growing body of literature has identified Treg cells as critical orchestrators of tissue protection during acute stress and as effector cells that drive repair following tissue injury. Despite substantial interest in these distinct roles, the field has struggled to disentangle Treg cell suppressive functions from those that promote tissue defense and repair. In this article, we will examine the literature in the context of specific physiologic settings, contrasting the suppressive function of Treg cells with their emerging roles in promoting tissue homeostasis and tissue repair. Further, we will discuss a new paradigm differentiating tissue defense from tissue repair-a paradigm needed to translate Treg cell-based therapies to the clinic.

Epigenetics and tissue immunity-Translating environmental cues into functional adaptations.

There is an increasing appreciation that many innate and adaptive immune cell subsets permanently reside within non-lymphoid organs, playing a critical role in tissue homeostasis and defense. The best characterized are macrophages and tissue-resident T lymphocytes that work in concert with organ structural cells to generate appropriate immune responses and are functionally shaped by organ-specific environmental cues. The interaction of tissue epithelial, endothelial and stromal cells is also required to attract, differentiate, polarize and maintain organ immune cells in their tissue niche. All of these processes require dynamic regulation of cellular transcriptional programmes, with epigenetic mechanisms playing a critical role, including DNA methylation and post-translational histone modifications. A failure to appropriately regulate immune cell transcription inevitably results in inadequate or inappropriate immune responses and organ pathology. Here, with a focus on the mammalian kidney, an organ which generates differing regional environmental cues (including hypersalinity and hypoxia) due to its physiological functions, we will review the basic concepts of tissue immunity, discuss the technologies available to profile epigenetic modifications in tissue immune cells, including those that enable single-cell profiling, and consider how these mechanisms influence the development, phenotype, activation and function of different tissue immune cell subsets, as well as the immunological function of structural cells.

Expression of NLRP3 and P2X7 transcripts in gingival tissues of chronic periodontitis patients and its correlation with P. gingivalis load and periodontal parameters

BackgroundInflammasomes are pivotal regulators of the host innate defense in periodontal tissues. Porphyromonas gingivalis modulates NLRP3 inflammasome complex and P2X7 receptor for survival in tissues through its virulence factors. AimTo estimate the expression of NLRP3 and P2X7 in gingival tissues of chronic periodontitis patients and to assess its correlation with periodontal clinical parameters and P. gingivalis load in subgingival plaque samples. Materials and methodsInterproximal gingival tissue and subgingival plaque samples (collected from same site) from systemically healthy chronic periodontitis patients (n = 22) and healthy controls (n = 22) were collected and stored in −80 °C. NLRP3 and P2X7 gene expression in gingival tissues and load of P. gingivalis in sub gingival plaque were assessed using real time Polymerase Chain Reaction. ResultsThe expression of NLRP3 in chronic periodontitis was marginally higher than healthy controls though the difference was statistically insignificant. P2X7 expression was higher in healthy controls and down regulated in chronic periodontitis patients (p = 0.04). A statistically significant correlation was observed between the probing pocket depth and expression of P2X7 gene in chronic periodontitis (p = 0.04). Correlation between P. gingivalis load and expression of the genes in tissues was either moderate (P2X7 control group) or negligible (both test and control of NLRP3). ConclusionA marginal increase in expression of NLRP3 and statistically significant decrease in P2X7 expression in chronic periodontitis patients was present. A statistically significant correlation was observed between P2X7 and P. gingivalis load in control group and periodontal parameters in test group. The study confirms involvement of genes in periodontal pathogenesis.

Obesity and its effects on the esophageal mucosal barrier.

Obesity is associated with gastroesophageal reflux disease (GERD) and its complications including reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. Traditionally, these associations have been attributed to the mechanical effect of abdominal fat in increasing intra-abdominal pressure, thereby promoting gastroesophageal reflux and causing disruption of antireflux mechanisms at the esophagogastric junction. However, recent studies suggest that visceral adipose tissue (VAT) produces numerous cytokines that can cause esophageal inflammation and impair esophageal mucosal barrier integrity through reflux-independent mechanisms that render the esophageal mucosa especially susceptible to GERD-induced injury. In this report, we review mechanisms of esophageal mucosal defense, the genesis and remodeling of visceral adipose tissue during obesity, and the potential role of substances produced by VAT, especially the VAT that encircles the esophagogastric junction, in the impairment of esophageal mucosal barrier integrity that leads to the development of GERD complications.

Signatures and Specificity of Tissue-Resident Lymphocytes Identified in Human Renal Peritumor and Tumor Tissue.

Tissue-resident memory T (TRM) cells are known to be important for the first line of defense in mucosa-associated tissues. However, the composition, localization, effector function, and specificity of TRM cells in the human kidney and their relevance for renal pathology have not been investigated. Lymphocytes derived from blood, renal peritumor samples, and tumor samples were phenotypically and functionally assessed by applying flow cytometry and highly advanced histology (multi-epitope ligand cartography) methods. CD69+CD103+CD8+ TRM cells in kidneys display an inflammatory profile reflected by enhanced IL-2, IL-17, and TNFα production, and their frequencies correlate with increasing age and kidney function. We further identified mucosa-associated invariant T and CD56dim and CD56bright natural killer cells likewise expressing CD69 and CD103, the latter significantly enriched in renal tumor tissues. CD8+ TRM cell frequencies were not elevated in kidney tumor tissue, but they coexpressed PD-1 and TOX and produced granzyme B. Tumor-derived CD8+ TRM cells from patients with metastases were functionally impaired. Both CD69+CD103-CD4+ and CD69+CD103-CD8+ TRM cells form distinct clusters in tumor tissues in proximity to antigen-presenting cells. Finally, EBV, CMV, BKV, and influenza antigen-specific CD8+ T cells were enriched in the effector memory T cell population in the kidney. Our data provide an extensive overview of TRM cells' phenotypes and functions in the human kidney for the first time, pointing toward their potential relevance in kidney transplantation and kidney disease.

Antioxidant compounds from Annona crassiflora fruit peel reduce lipid levels and oxidative damage and maintain the glutathione defense in hepatic tissue of Triton WR-1339-induced hyperlipidemic mice

Dyslipidemia is a risk factor for the pathogenesis of several diseases, such as obesity, hypertension, atherosclerosis and cardiovascular diseases. In addition to interfering with serum concentrations of cholesterol and triglycerides, hyperlipidemia is involved in oxidative stress increase and reduction of the endogenous antioxidant defenses. The fruit peel of Annona crassiflora crude extract (CEAc) and its polyphenols-rich fraction (PFAc) were investigated against hypertriglyceridemia, hypercholesterolemia and hepatic oxidative stress in Triton WR-1339-induced hyperlipidemic mice. Lipid parameters in serum, feces and liver, as well as hepatic oxidative status, and enzymatic and non-enzymatic antioxidant defense systems were analyzed. Pre-treatment with CEAc for 12 days decreased hepatic triglycerides and total cholesterol, and similar to PFAc, increased the high-density lipoprotein level. There were reductions in lipid peroxidation and protein carbonylation, as well as restoration of the glutathione defense system and total thiol content in the liver of the hyperlipidemic mice treated with PFAc. The fruit peel of A. crassiflora, a promising natural source of bioactive molecules, showed a potential lipid-lowering action and hepatoprotective activities triggered by reduction of oxidative damage and maintenance of the enzymatic and non-enzymatic antioxidant systems impaired by the hyperlipidemic state.

Effect of Probiotics Lactobacillus acidophilus and Lacticaseibacillus rhamnosus on Antibacterial Response Gene Transcription of Human Peripheral Monocytes.

Periodontitis and related systemic inflammatory diseases are characterized by imbalanced ratio between pro- and anti-inflammatory factors. Probiotics may control inflammation by altering the inflammatory phenotype of defense cells. We aimed to evaluate the gene transcription of the antibacterial response of monocytes to exposure to probiotic lactobacilli. CD14 + monocytes were obtained by positive selection from peripheral blood mononuclear cells from healthy donors (5 × 104 CD14 + /mL) and cultured with probiotic strains of Lacticaseibacillus rhamnosus (LR-32) and Lactobacillus acidophilus (LA-5) at a 1:10 multiplicity of infection in 24-well plates for 12h. The gene expression analysis was performed by RT-qPCR using the Kit RT2 human antibacterial response, and in the supernatant, the cytokines were determined by ELISA. Tukey's post hoc test following an ANOVA with a p value of 5% was used for statistical analysis. Both probiotic strains increased the levels of cytokines TNF-α and CXCL-8 in the supernatant compared to the control of non-challenged cells (p < 0.05), but for IL-1Β and IL-6, this effect was observed only for LA-5 (p < 0.05). The fold-regulation values for the following genes for LA-5 and LR-32 were, respectively, IL-12B (431.94 and 33.30), IL-1Β (76.73 and 17.14), TNF-α (94.63 and 2.49), CXCL-8 (89.59 and 4.18), and TLR-2 (49.68 and 3.40). Likewise, most of the other genes evaluated showed greater expression for LA-5 compared to LR-32 (p < 0.05). The positive regulation of inflammatory factors such as IL-1β promoted by L. acidophilus LA-5 may increase the antibacterial activity of innate defense in periodontal tissues. However, this property may be deleterious by increasing inflammatory response.

A Targetable, Noncanonical Signal Transducer and Activator of Transcription 3 Activation Induced by the Y-Less Region of IL-22 Receptor Orchestrates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice

Exacerbated IL-22 activity induces tissue inflammation and immune disorders such as psoriasis. However, because IL-22 is also essential for tissue repair and defense at barrier interfaces, targeting IL-22 activity to treat psoriasis bears the risk of deleterious effects at mucosal sites such as the gut. We previously showed invitro that IL-22 signaling relies on IL-22 receptor alpha (IL-22Rα) Y-dependent and -independent pathways. The second depends on the C-terminal Y-less region of IL-22Rα and leads to a massive signal transducer and activator of transcription 3 (STAT3) activation. Because STAT3 activation is associated with the development of psoriasis, we hypothesized that the specific inhibition of the noncanonical STAT3 activation by the Y-less region of IL-22Rα could reduce psoriasis-like disease while leaving intact its tissue defense functions in the gut. We show that mice expressing a C-terminally truncated version of IL-22Rα (ΔCtermut/mut mice) are protected from the development of psoriasis-like dermatitis lesions induced by imiquimod to a lesser extent than Il22ra-/- mice. In contrast, only Il22ra-/- mice lose weight after Citrobacter rodentium infection. Altogether, our data suggest that specific targeting of the noncanonical STAT3 activation by IL-22 could serve to treat psoriasis-like skin inflammation without affecting IL-22‒dependent tissue repair or barrier defense at other sites.

Neuroimmune interactions in peripheral tissues

Neuroimmune interactions have been revealed to be at the centre stage of tissue defence, organ homeostasis, and organismal physiology. Neuronal and immune cell subsets have been shown to colocalize in discrete tissue environments, forming neuroimmune cell units that constitute the basis for bidirectional interactions. These multitissue units drive coordinated neuroimmune responses to local and systemic signals, which represents an important challenge to our current views of mucosal physiology and immune regulation. In this review, we focus on the impact of reciprocal neuroimmune interactions, focusing on the anatomy of neuronal innervation and on the neuronal regulation of immune cells in peripheral tissues. Finally, we shed light on recent studies that explore how neuroimmune interactions maximise sensing and integration of environmental aggressions, modulating immune function in health and disease.

Comparative Phenotypic and Functional Analyses of the Effects of IL-10 or TGF-β on Porcine Macrophages.

Simple SummaryMacrophages play a central role in innate immune response to both infectious and non-infectious stressors. They respond to different agonists modifying their phenotype and functions. In humans and mice, the regulatory cytokines IL-10 or TGF-β are both known to drive macrophage polarization into an anti-inflammatory phenotype, referred to as M2c. However, the immune systems of animal species each have their own peculiarities and the M2c subsets has never been investigated in pigs. A deep knowledge of the porcine immune system is required to design vaccines or control strategies against pathogens, which are a major constraint to pork production. Due to anatomical, physiological, and immunological similarities, swine are attracting increasing attention as a model for human diseases. To better characterize porcine macrophages, we evaluated the effects of IL-10 or TGF-β on the phenotype and function of monocyte-derived macrophages. Both cytokines downregulated the expression of MHC II DR and CD14. IL-10, but not TGF-β, statistically significantly reduced the ability of macrophages to respond to Toll-like receptor 2 (TLR2) or TLR4 agonists. Whilst these data suggest differentiation to an M2c-like immunosuppressive phenotype, the responses, and differences between IL-10 and TGF-β also reveals species-specific differences.Macrophages are phagocytic cells involved in maintaining tissue homeostasis and defense against pathogens. Macrophages may be polarized into different functionally specialized subsets. M2c macrophages arise following stimulation with IL-10 or TGF-β and mediate anti-inflammatory and tissue repair functions. M2c macrophages remain poorly characterized in the pig, thus we investigated the impact of these regulatory cytokines on porcine monocyte-derived macrophages (moMΦ). The phenotype and functionality of these cells was characterized though confocal microscopy, flow cytometry, ELISA, and RT-qPCR. Both cytokines induced CD14 and MHC II DR down-regulation and reduced IL-6, TNF-α, and CD14 expression, suggestive of an anti-inflammatory phenotype. Interestingly, neither IL-10 or TGF-β were able to trigger IL-10 induction or release by moMΦ. Differences between these cytokines were observed: stimulation with IL-10, but not TGF-β, induced up-regulation of both CD16 and CD163 on moMΦ. In addition, IL-10 down-regulated expression of IL-1β and IL-12p40 4h post-stimulation and induced a stronger impairment of moMΦ ability to respond to either TLR2 or TLR4 agonists. Overall, our results provide an overview of porcine macrophage polarization by two immunosuppressive cytokines, revealing differences between IL-10 and TGF-β, and reporting some peculiarity of swine, which should be considered in translational studies.