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Frontiers in Endocrinology 2022Macrophages, the main immune cells in the skin, form an innate immune barrier. Under physiological conditions, skin maintains immune barrier function through macrophage...
Macrophages, the main immune cells in the skin, form an innate immune barrier. Under physiological conditions, skin maintains immune barrier function through macrophage phagocytosis and antigen presentation. Parenchymal and stromal cell regeneration plays an important role in skin injury repair and uses macrophage plasticity to influence and stabilize the skin microenvironment. Diabetic skin lesions are the most common diabetes complication and are involved in the early pathophysiology of diabetic foot. Therefore, studying the initial link in diabetic skin lesions is a research hot spot in the early pathogenesis of diabetic foot. Skin inflammation caused by hyperglycaemia, oxidative stress and other injuries is an important feature, but the specific mechanism is unknown. Recent studies have suggested that chronic inflammatory injury is widely involved in a variety of skin diseases, and whether it plays an important role in diabetic skin lesions is unclear. In this review, current research hotspots were combined with the pathogenesis of diabetic skin lesions and analysed from the perspectives of the physiological function of skin macrophages, the impairment of skin macrophages in diabetes, and the mechanism of chronic inflammatory injury in macrophages to provide a theoretical basis for early screening and evaluation of diabetic foot.
Topics: Diabetes Mellitus; Diabetic Foot; Humans; Hyperglycemia; Inflammation; Macrophages; Skin
PubMed: 36093074
DOI: 10.3389/fendo.2022.960551 -
Experimental Gerontology Jul 2022Resistance exercise is beneficial for the immune system, including decreased susceptibility to infections and improved effectiveness of vaccinations. This review aims to...
BACKGROUND
Resistance exercise is beneficial for the immune system, including decreased susceptibility to infections and improved effectiveness of vaccinations. This review aims to provide a systematic analysis of the literature regarding the impact of resistance exercise on immune cells in the blood circulation.
MATERIALS AND METHODS
The protocol of this review followed the PRISMA guidelines and registered in PROSPERO (ID: CRD42020157834). PubMed and Web-of-Science were systematically searched for relevant articles. Outcomes were divided into two categories: 1) inflammatory gene expression or secretion of inflammation-related cytokines and 2) other aspects such as cell migration, proliferation, apoptosis, phagocytosis, and redox status.
RESULTS
Thirty intervention studies were included in this review, of which 11 articles were randomized controlled trials and six non-randomized controlled trials. Although only resistance exercise interventions were included, there was a high heterogeneity regarding specific exercise modalities. The most frequently studied outcome measures were the gene and protein expression levels in peripheral blood mononuclear cells (PBMC). This review reveals that already one acute exercise bout activates the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway in PBMC. Although resistance exercise induces an acute cytosolic oxidative stress response, the antioxidant enzyme expression is improved after resistance training period. Natural killer cell activity increases in older but decreases in younger adults immediately after a resistance exercise bout. Moreover, resistance exercise improves neutrophil phagocytic activity. Finally, effects on lymphocyte proliferation remain unclear.
CONCLUSIONS
The results of this systematic review demonstrate that resistance exercise has beneficial effects on several aspects of immune cell function both in young and older individuals. Acute changes in immune cell function occur already after a single bout of resistance exercise. However, regular resistance training during several weeks seems necessary to obtain beneficial adaptations that can be related to better immunity and reduced inflammation. The effects documented in this review confirm the beneficial effects of resistance exercise in young as well as older persons on the immune cell function.
Topics: Aged; Aged, 80 and over; Cytokines; Exercise; Humans; Inflammation; Leukocytes, Mononuclear; Randomized Controlled Trials as Topic; Resistance Training
PubMed: 35490790
DOI: 10.1016/j.exger.2022.111822 -
Frontiers in Immunology 2022Cardiovascular diseases, the notorious killer, are mainly caused by atherosclerosis (AS) characterized by lipids, cholesterol, and iron overload in plaques. Macrophages...
Cardiovascular diseases, the notorious killer, are mainly caused by atherosclerosis (AS) characterized by lipids, cholesterol, and iron overload in plaques. Macrophages are effector cells and accumulate to the damaged and inflamed sites of arteries to internalize native and chemically modified lipoproteins to transform them into cholesterol-loaded foam cells. Foam cell formation is determined by the capacity of phagocytosis, migration, scavenging, and the features of phenotypes. Macrophages are diverse, and the subsets and functions are controlled by their surrounding microenvironment. Generally, macrophages are divided into classically activated (M1) and alternatively activated (M2). Recently, intraplaque macrophage phenotypes are recognized by the stimulation of CXCL4 (M4), oxidized phospholipids (Mox), hemoglobin/haptoglobin complexes [HA-mac/M(Hb)], and heme (Mhem). The pro-atherogenic or anti-atherosclerotic phenotypes of macrophages decide the progression of AS. Besides, apoptosis, necrosis, ferroptosis, autophagy and pyrotopsis determine plaque formation and cardiovascular vulnerability, which may be associated with macrophage polarization phenotypes. In this review, we first summarize the three most popular hypotheses for AS and find the common key factors for further discussion. Secondly, we discuss the factors affecting macrophage polarization and five types of macrophage death in AS progression, especially ferroptosis. A comprehensive understanding of the cellular and molecular mechanisms of plaque formation is conducive to disentangling the candidate targets of macrophage-targeting therapies for clinical intervention at various stages of AS.
Topics: Atherosclerosis; Foam Cells; Humans; Macrophage Activation; Macrophages; Plaque, Atherosclerotic
PubMed: 35432323
DOI: 10.3389/fimmu.2022.843712 -
Frontiers in Immunology 2021Congenital infection of the fetus trans-placental passage of pathogens can result in severe morbidity and mortality. Even without transmission to the fetus, infection...
BACKGROUND
Congenital infection of the fetus trans-placental passage of pathogens can result in severe morbidity and mortality. Even without transmission to the fetus, infection of the placenta itself is associated with pregnancy complications including pregnancy loss and preterm birth. Placental macrophages, also termed Hofbauer cells (HBCs), are fetal-origin macrophages residing in the placenta that are likely involved in responding to placental infection and protection of the developing fetus. As HBCs are the only immune cell present in the villous placenta, they represent one of the final opportunities for control of infection and prevention of passage to the developing fetus.
OBJECTIVE AND RATIONALE
The objective of this review was to provide a systematic overview of the literature regarding HBC responses during infection in pregnancy, including responses to viral, bacterial, and parasitic pathogens.
METHODS
PubMed and Scopus were searched on May 20th, 2021, with no limit on publication date, to identify all papers that have studied placental macrophages/Hofbauer cells in the context of infection. The following search strategy was utilized: (hofbauer* OR "hofbauer cells" OR "hofbauer cell" OR "placental macrophage" OR "placental macrophages") AND [infect* OR virus OR viral OR bacteri* OR parasite* OR pathogen* OR LPS OR "poly(i:c)" OR toxoplasm* OR microb* OR HIV)].
OUTCOMES
86 studies were identified for review. This included those that investigated HBCs in placentas from pregnancies complicated by maternal infection and studies investigating HBC responses to pathogens or Pathogen-Associated Molecular Patterns (PAMPs). HBCs can be infected by a variety of pathogens, and HBC hyperplasia was a common observation. HBCs respond to pathogen infection and PAMPs by altering their transcriptional, translational and secretion profiles. Co-culture investigations demonstrate that they can replicate and transmit pathogens to other cells. In other cases, they may eliminate the pathogen through a variety of mechanisms including phagocytosis, cytokine-mediated pathogen elimination, release of macrophage extracellular traps and HBC-antibody-mediated neutralization. HBC responses differ across gestation and may be influenced by pre-existing immunity. Clinical information, including gestational age at infection, gestational age of the samples, mode of sample collection and pregnancy outcome were missing for the majority of studies.
Topics: Female; Fetus; Humans; Infant, Newborn; Macrophages; Pathogen-Associated Molecular Pattern Molecules; Placenta; Pregnancy; Premature Birth
PubMed: 35250964
DOI: 10.3389/fimmu.2021.756035 -
World Journal of Gastrointestinal... Nov 2021The omentum is an organ that is easily sacrificed during abdominal surgery. The scope of omentectomy and whether a routine omentectomy should be performed are still...
BACKGROUND
The omentum is an organ that is easily sacrificed during abdominal surgery. The scope of omentectomy and whether a routine omentectomy should be performed are still unknown.
AIM
To review the literature in order to determine the physiological functions of the omentum and the roles it plays in pathological events in order to reveal the necessity for removal and preservation of the omentum.
METHODS
A clinical review of the English language literature based on the MEDLINE (PubMed) database was conducted using the keywords: "abdomen", "gastrointestinal", "tumor", "inflammation", "omental flap", "metastasis", "omentum", and "omentectomy". In addition, reports were also identified by systematically reviewing all references in retrieved papers.
RESULTS
The omentum functions as a natural barrier in areas where pathological processes occur in the abdominal cavity. The omentum limits and controls inflammatory and infectious pathologies that occur in the abdomen. It also aids in treatment due to its cellular functions including lymphatic drainage and phagocytosis. It shows similar behavior in tumors, but it cannot cope with increasing tumor burden. The stage of the disease changes due to the tumor mass it tries to control. Therefore, it is considered an indicator of poor prognosis. Due to this feature, the omentum is one of the first organs to be sacrificed during surgical procedures. However, there are many unknowns regarding the role and efficacy of the omentum in cancer.
CONCLUSION
The omentum is a unique organ that limits and controls inflammatory processes, foreign masses, and lesions that develop in the abdominal cavity. Omental flaps can be used in all anatomical areas, including the thorax, abdomen, pelvis, and extremities. The omentum is an organ that deserves the title of the abdominal policeman. It is generally accepted that the omentum should be removed in cases where there is tumor invasion. However, the positive or negative contribution of omental resection in the treatment of abdominal pathologies should be questioned.
PubMed: 34950436
DOI: 10.4240/wjgs.v13.i11.1497 -
Frontiers in Immunology 2021Trypanosomatids are protozoa responsible for a wide range of diseases, with emphasis on Chagas Disease (CD) and Leishmaniasis, which are in the list of most relevant...
Methodological Appraisal of Literature Concerning the Analysis of Genetic Variants or Protein Levels of Complement Components on Susceptibility to Infection by Trypanosomatids: A Systematic Review.
BACKGROUND
Trypanosomatids are protozoa responsible for a wide range of diseases, with emphasis on Chagas Disease (CD) and Leishmaniasis, which are in the list of most relevant Neglected Tropical Diseases (NTD) according to World Health Organization (WHO). During the infectious process, immune system is immediately activated, and parasites can invade nucleated cells through a broad diversity of receptors. The complement system - through classical, alternative and lectin pathways - plays a role in the first line of defense against these pathogens, acting in opsonization, phagocytosis and lysis of parasites. Genetic modifications in complement genes, such as Single Nucleotide Polymorphisms (SNPs), can influence host susceptibility to these parasites and modulate protein expression.
METHODS
In March and April 2021, a literature search was conducted at the PubMed and Google Scholar databases and the reference lists obtained were verified. After applying the inclusion and exclusion criteria, the selected studies were evaluated and scored according to eleven established criteria regarding their thematic approach and design, aiming at the good quality of publications.
RESULTS
Twelve papers were included in this systematic review: seven investigating CD and five focusing on Leishmaniasis. Most articles presented gene and protein approaches, careful determination of experimental groups, and adequate choice of experimental techniques, although several of them were not up-to-date. Ten studies explored the association of polymorphisms and haplotypes with disease progression, with emphasis on lectin complement pathway genes. Decreased and increased patient serum protein levels were associated with susceptibility to CD and Visceral Leishmaniasis, respectively.
CONCLUSION
This systematic review shows the influence of genetic alterations in complement genes on the progression of several infectious diseases, with a focus on conditions caused by trypanosomatids, and contributes suggestions and evidence to improve experimental design in future research proposals.
Topics: Chagas Disease; Complement Activation; Complement System Proteins; Disease Progression; Genetic Predisposition to Disease; Genetic Variation; Host-Parasite Interactions; Humans; Leishmania; Leishmaniasis; Phenotype; Risk Assessment; Risk Factors; Trypanosoma cruzi
PubMed: 34899745
DOI: 10.3389/fimmu.2021.780810 -
Autoimmunity Reviews Feb 2022Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease that is common in elderly people. Its classification in the spectrum of autoinflammatory and autoimmune... (Review)
Review
BACKGROUND AND AIM
Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease that is common in elderly people. Its classification in the spectrum of autoinflammatory and autoimmune diseases is difficult because of its only partially understood immune-mediated mechanisms. The literature concerning the innate and adaptive immune system activation in PMR was systematically reviewed highlighting the relative weight of autoinflammation and autoimmunity in its pathogenesis and disease progression.
METHODS
A literature search on PubMed Central and Embase scientific databases was performed by two independent reviewers. To be eligible, the studies needed to fully satisfy our initial PICO framework: a primary diagnosis of PMR as a population, the search for immune/inflammatory cells, cytokines and autoantibodies as an intervention, a control group consisting in healthy controls, patients with other inflammatory rheumatic diseases or PMR patients in remission after treatment and as outcomes the results of the investigations in the analyzed tissue samples. The most relevant data of the included papers were extracted by using a standardized template.
RESULTS
Of the 933 screened abstracts, 52 papers were included in the systematic review and categorized depending on their primary research objectives. The hyper-activity of neutrophils and monocytes, expressing toll-like receptor 7 in active disease, an impaired phagocytosis and endothelial dysfunction, as well as an increased count of innate T cells in patients with remission emerged among the major derangements of the innate immune response in PMR. Among the cytokines profile, interleukin-6 plays a key role but other pro-inflammatory mediators and angiogenesis markers such as chemokines, B-cell activating factor, vascular endothelial growth factor and angiopoietins seem to be involved in refractory or glucocorticoid-resistant PMR. The aberrant adaptive immune response was documented by tissue and serum findings of polarized T cells towards T helper 1 and 17 phenotypes, an increased expression of immunosenescent surface markers and a downregulated immunoregulatory response. The altered distribution of peripheral B cells, detected during active disease, suggested their peripheral migration towards unidentified sites. The interaction between innate and adaptive immune response was documented by a synovial infiltrate of macrophages and T cells. Despite multiple autoantibodies have been detected in PMR patients, none proved to correlate with disease activity seeming to be reactive to the marked inflammation or antigenic determinants provided by environmental triggers or tissue/cell damage.
CONCLUSIONS
The complex network between innate and adaptive immune system in PMR is supported by findings at molecular and cellular levels. By considering both the ends of the pathophysiological spectrum of immune-mediated rheumatic diseases, PMR may be regarded as an inflammatory immune-mediated disease with mixed mechanisms in a background of genetic and epigenetic factors together with immunological and endocrine senescence.
Topics: Autoimmunity; Giant Cell Arteritis; Humans; Neutrophils; Polymyalgia Rheumatica
PubMed: 34798314
DOI: 10.1016/j.autrev.2021.102995 -
Frontiers in Immunology 2021The global prevalence and recurrence rate of kidney stones is very high. Recent studies of Randall plaques and urinary components , and including gene manipulation,...
BACKGROUND
The global prevalence and recurrence rate of kidney stones is very high. Recent studies of Randall plaques and urinary components , and including gene manipulation, have attempted to reveal the pathogenesis of kidney stones. However, the evidence remains insufficient to facilitate the development of novel curative therapies. The involvement of renal and peripheral macrophages in inflammatory processes offers promise that might lead to the development of therapeutic targets. The present systematic literature review aimed to determine current consensus about the functions of macrophages in renal crystal development and suppression, and to synthesize evidence to provide a basis for future immunotherapy.
METHODS
We systematically reviewed the literature during February 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles investigating the relationship between macrophages and urolithiasis, particularly calcium oxalate (CaOx) stones, were extracted from PubMed, MEDLINE, Embase, and Scopus. Study subjects, languages, and publication dates were unrestricted. Two authors searched and screened the publications.
RESULTS
Although several studies have applied mixed modalities, we selected 10, 12, and seven (total, n = 29) of 380 articles that respectively described cultured cells, animal models, and human samples.The investigative trend has shifted to macrophage phenotypes and signaling pathways, including micro (m)-RNAs since the discovery of macrophage involvement in kidney stones in 1999. Earlier studies of mice-associated macrophages with the acceleration and suppression of renal crystal formation. Later studies found that pro-inflammatory M1- and anti-inflammatory M2-macrophages are involved. Studies of human-derived and other macrophages and showed that M2-macrophages (stimulated by CSF-1, IL-4, and IL-13) can phagocytose CaOx crystals, which suppresses stone development. The signaling mechanisms that promote M2-like macrophage polarization toward CaOx nephrocalcinosis, include the NLRP3, PPARγ-miR-23-Irf1/Pknox1, miR-93-TLR4/IRF1, and miR-185-5p/CSF1 pathways.Proteomic findings have indicated that patients who form kidney stones mainly express M1-like macrophage-related proteins, which might be due to CaOx stimulation of the macrophage exosomal pathway.
CONCLUSIONS
This systematic review provides an update regarding the current status of macrophage involvement in CaOx nephrolithiasis. Targeting M2-like macrophage function might offer a therapeutic strategy with which to prevent stones crystal phagocytosis.
Topics: Animals; Calcium Oxalate; Humans; Kidney Calculi; Macrophages; Nephrolithiasis
PubMed: 34108970
DOI: 10.3389/fimmu.2021.673690 -
Neurobiology of Disease Feb 2021Neurodegenerative disorders such as Alzheimer's disease (AD), Lewy body diseases (LBD), and the amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD)... (Meta-Analysis)
Meta-Analysis
Neurodegenerative disorders such as Alzheimer's disease (AD), Lewy body diseases (LBD), and the amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) spectrum are defined by the accumulation of specific misfolded protein aggregates. However, the mechanisms by which each proteinopathy leads to neurodegeneration remain elusive. We hypothesized that there is a common "pan-neurodegenerative" gene expression signature driving pathophysiology across these clinically and pathologically diverse proteinopathies. To test this hypothesis, we performed a systematic review of human CNS transcriptomics datasets from AD, LBD, and ALS-FTD patients and age-matched controls in the Gene Expression Omnibus (GEO) and ArrayExpress databases, followed by consistent processing of each dataset, meta-analysis, pathway enrichment, and overlap analyses. After applying pre-specified eligibility criteria and stringent data pre-processing, a total of 2600 samples from 26 AD, 21 LBD, and 13 ALS-FTD datasets were included in the meta-analysis. The pan-neurodegenerative gene signature is characterized by an upregulation of innate immunity, cytoskeleton, and transcription and RNA processing genes, and a downregulation of the mitochondrial electron transport chain. Pathway enrichment analyses also revealed the upregulation of neuroinflammation (including Toll-like receptor, TNF, and NFκB signaling) and phagocytosis, and the downregulation of mitochondrial oxidative phosphorylation, lysosomal acidification, and ubiquitin-proteasome pathways. Our findings suggest that neuroinflammation and a failure in both neuronal energy metabolism and protein degradation systems are consistent features underlying neurodegenerative diseases, despite differences in the extent of neuronal loss and brain regions involved.
Topics: Alzheimer Disease; Amyotrophic Lateral Sclerosis; Brain; Energy Metabolism; Frontotemporal Dementia; Humans; Inflammation; Inflammation Mediators; Lewy Body Disease; Neurodegenerative Diseases; Proteostasis; Transcriptome
PubMed: 33347974
DOI: 10.1016/j.nbd.2020.105225