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Veterinary Sciences Jun 2024Traditionally, non- staphylococci and mammaliicocci (NASM) were not considered significant players in bovine mastitis. This study investigated the involvement of NASM (...
Traditionally, non- staphylococci and mammaliicocci (NASM) were not considered significant players in bovine mastitis. This study investigated the involvement of NASM ( and ) and lactic acid bacteria (LAB) strains () through bovine neutrophil responses. Bovine neutrophils displayed minimal apoptosis upon NASM and LAB challenge. Neutrophils expressed high TLR2 after challenge, but TLR6 expression varied and remained low in NASM pathogen recognition. Bovine neutrophils effectively engulfed and killed LAB, but their activity was significantly impaired against NASM. This was evident in , where reduced TLR6 recognition and a weakened phagocytic response likely contributed to a lower bactericidal effect. Regardless of the bacteria encountered, intracellular ROS production remained high. -challenged neutrophils displayed upregulation in genes for pathogen recognition (TLRs), ROS production, and both pro- and anti-apoptotic pathways. This response mirrored that of . except for and , suggesting these bacteria have divergent roles in triggering cell death. Our findings suggest that manipulates bovine neutrophil defenses through coordinated changes in functional responses and gene expression, while LAB strains have a weaker influence on apoptosis.
PubMed: 38922009
DOI: 10.3390/vetsci11060262 -
Pathogens (Basel, Switzerland) May 2024Coronavirus frequently infects humans and animals, showing the ability to recombine and cross over to different species. Cats can be considered a model for studying...
Coronavirus frequently infects humans and animals, showing the ability to recombine and cross over to different species. Cats can be considered a model for studying coronavirus infection, in which feline coronavirus (FCoV) represents a major enteric pathogen related to gastroenteric disease. In this animal, the virus can acquire tropism for macrophage cells, leading to a deadly disease called feline infectious peritonitis (FIP). In this study, monocyte-derived macrophages were isolated by CD14-positive selection in venous whole blood from 26 cats with FIP and 32 FCoV-positive healthy cats. Phagocytosis and respiratory burst activities were investigated and compared between the groups. This is the first study comparing macrophage activity in cats affected by FIP and healthy cats positive for FCoV infection. Our results showed that in cats with FIP, the phagocytic and respiratory burst activities were significantly lower. Our results support the possible role of host immunity in Coronaviridae pathogenesis in cats, supporting future research on the immune defense against this systemic disease.
PubMed: 38921735
DOI: 10.3390/pathogens13060437 -
Marine Drugs Jun 2024SeviL, a galactoside-binding lectin previously isolated from the mussel , was demonstrated to trigger apoptosis in HeLa ovarian cancer cells. Here, we show that this...
SeviL, a galactoside-binding lectin previously isolated from the mussel , was demonstrated to trigger apoptosis in HeLa ovarian cancer cells. Here, we show that this lectin can promote the polarization of macrophage cell lines toward an M1 functional phenotype at low concentrations. The administration of SeviL to monocyte and basophil cell lines reduced their growth in a dose-dependent manner. However, low lectin concentrations induced proliferation in the RAW264.7 macrophage cell line, which was supported by the significant up-regulation of TOM22, a component of the mitochondrial outer membrane. Furthermore, the morphology of lectin-treated macrophage cells markedly changed, shifting from a spherical to an elongated shape. The ability of SeviL to induce the polarization of RAW264.7 cells to M1 macrophages at low concentrations is supported by the secretion of proinflammatory cytokines and chemokines, as well as by the enhancement in the expression of IL-6- and TNF-α-encoding mRNAs, both of which encode inflammatory molecular markers. Moreover, we also observed a number of accessory molecular alterations, such as the activation of MAP kinases and the JAK/STAT pathway and the phosphorylation of platelet-derived growth factor receptor-α, which altogether support the functional reprogramming of RAW264.7 following SeviL treatment. These results indicate that this mussel β-trefoil lectin has a concentration-dependent multifunctional role in regulating cell proliferation, phenotype, and death in macrophages, suggesting its possible involvement in regulating hemocyte activity in vivo.
Topics: Animals; Mice; Macrophages; RAW 264.7 Cells; Lectins; Bivalvia; Cell Proliferation; Humans; Cytokines; Phenotype; Signal Transduction
PubMed: 38921580
DOI: 10.3390/md22060269 -
Journal of Functional Biomaterials May 2024Yeasts resistant to antifungals have become an increasing risk to human health. One of the best antimicrobial properties is reported to be present in silver...
Yeasts resistant to antifungals have become an increasing risk to human health. One of the best antimicrobial properties is reported to be present in silver nanoparticles (AgNPs); however, little is known about the antimicrobial potential of AgNPs produced using thermophilic bacteria. How AgNPs cause cell death is different depending on the type of the cell, and the mode of death induced is cell-type specific. Apoptosis, one of the types of regulated cell death, can be extremely useful in the fight against infection because surrounding cells that have phagocytic activity can efficiently absorb the apoptotic bodies formed during apoptosis. In the course of this work, for the first time, comprehensive antifungal studies of AgNPs were performed using thermophilic spp. bacteria against , also with the addition of the model yeast . The determined minimal inhibitory concentrations (MICs) were 10 μg/mL against and 50 μg/mL against for sp. strain 25 AgNPs, and for sp. 612 the MICs were 5 μg/mL and 25 μg/mL, respectively. It was shown for the first time that the exposure of the yeast cells leads to caspase activation in both and after exposure to spp. AgNPs. Also, a statistically significant change in the number of cells with permeable membranes was detected. Moreover, it was shown that the antimicrobial effect of the AgNPs is related to ROS generation and lipid peroxidation in yeast.
PubMed: 38921516
DOI: 10.3390/jfb15060142 -
Current Oncology (Toronto, Ont.) Jun 2024Neuroblastoma is a pediatric cancer with significant clinical heterogeneity. Despite extensive efforts, it is still difficult to cure children with high-risk... (Review)
Review
Neuroblastoma is a pediatric cancer with significant clinical heterogeneity. Despite extensive efforts, it is still difficult to cure children with high-risk neuroblastoma. Immunotherapy is a promising approach to treat children with this devastating disease. We have previously reported that macrophages are important effector cells in high-risk neuroblastoma. In this perspective article, we discuss the potential function of the macrophage inhibitory receptor SIRPA in the homeostasis of tumor-associated macrophages in high-risk neuroblastoma. The ligand of SIRPA is CD47, known as a "don't eat me" signal, which is highly expressed on cancer cells compared to normal cells. CD47 is expressed on both tumor and stroma cells, whereas SIRPA expression is restricted to macrophages in high-risk neuroblastoma tissues. Notably, high expression is associated with better disease outcome. According to the current paradigm, the interaction between CD47 on tumor cells and SIRPA on macrophages leads to the inhibition of tumor phagocytosis. However, data from recent clinical trials have called into question the use of anti-CD47 antibodies for the treatment of adult and pediatric cancers. The restricted expression of SIRPA on macrophages in many tissues argues for targeting SIRPA on macrophages rather than CD47 in CD47/SIRPA blockade therapy. Based on the data available to date, we propose that disruption of the CD47-SIRPA interaction by anti-CD47 antibody would shift the macrophage polarization status from M1 to M2, which is inferred from the 1998 study by Timms et al. In contrast, the anti-SIRPA F(ab') lacking Fc binds to SIRPA on the macrophage, mimics the CD47-SIRPA interaction, and thus maintains M1 polarization. Anti-SIRPA F(ab') also prevents the binding of CD47 to SIRPA, thereby blocking the "don't eat me" signal. The addition of tumor-opsonizing and macrophage-activating antibodies is expected to enhance active tumor phagocytosis.
Topics: CD47 Antigen; Humans; Neuroblastoma; Receptors, Immunologic; Antigens, Differentiation; Macrophages
PubMed: 38920727
DOI: 10.3390/curroncol31060243 -
Cells Jun 2024Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies...
BACKGROUND
Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies between individuals and over the course of the disease. Recognising the clinicopathological features that most strongly associate with disease outcomes will inform future efforts at patient phenotyping.
AIMS
We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropathological features in an autopsy cohort of progressive MS.
METHODS
Sequential sections of frontal, cingulate and occipital cortex, thalamus, brain stem (pons) and cerebellum including dentate nucleus (n = 35 progressive MS, females = 28, males = 7; age died = 53.5 years; range 38-98 years) were immunostained for myelin (anti-MOG), neurons (anti-HuC/D) and microglia/macrophages (anti-HLA). The extent of demyelination, neurodegeneration, the presence of active and/or chronic active lesions and quantification of brain and leptomeningeal inflammation was captured by digital pathology.
RESULTS
Digital analysis of tissue sections revealed the variable extent of pathology that characterises progressive MS. Microglia/macrophage activation, if found at a higher level in a single block, was typically elevated across all sampled blocks. Compartmentalised (perivascular/leptomeningeal) inflammation was associated with age-related measures of disease severity and an earlier death.
CONCLUSION
Digital pathology identified prognostically important clinicopathological correlations in MS. This methodology can be used to prioritise the principal pathological processes that need to be captured by future MS biomarkers.
Topics: Humans; Middle Aged; Female; Male; Multiple Sclerosis; Aged; Adult; Biomarkers; Aged, 80 and over; Inflammation; Brain; Microglia; Macrophages
PubMed: 38920650
DOI: 10.3390/cells13121020 -
Cells Jun 2024causes 6.4 million cases of tuberculosis and claims 1.6 million lives annually. Mycobacterial adhesion, invasion of host cells, and subsequent intracellular survival...
causes 6.4 million cases of tuberculosis and claims 1.6 million lives annually. Mycobacterial adhesion, invasion of host cells, and subsequent intracellular survival are crucial for the infection and dissemination process, yet the cellular mechanisms underlying these phenomena remain poorly understood. This study created a (BCG) transposon library using a MycomarT7 phage carrying a Himar1 Mariner transposon to identify genes related to mycobacteria adhesion and invasion. Using adhesion and invasion model screening, we found that the mutant strain B2909 lacked adhesion and invasion abilities because of an inactive gene, which encodes a fatty-acyl CoA ligase, although the specific function of this gene remains unclear. To investigate the role of FadD18, we constructed a complementary strain and observed that expression enhanced the colony size and promoted the formation of a stronger cord-like structure; FadD18 expression also inhibited BCG growth and reduced BCG intracellular survival in macrophages. Furthermore, FadD18 expression elevated levels of the proinflammatory cytokines IL-6, IL-1β, and TNF-α in infected macrophages by stimulating the NF-κB and MAPK signaling pathways. Overall, the FadD18 plays a key role in the adhesion and invasion abilities of mycobacteria while modulating the intracellular survival of BCG by influencing the production of proinflammatory cytokines.
Topics: Mycobacterium tuberculosis; Cytokines; Macrophages; Mycobacterium bovis; Mice; Bacterial Proteins; Animals; Humans; NF-kappa B; Microbial Viability; Bacterial Adhesion
PubMed: 38920649
DOI: 10.3390/cells13121019 -
Biosensors Jun 2024Current quantitative gene expression detection in genomic and transcriptomic research heavily relies on quantitative real-time PCR (qPCR). While existing multiplex gene...
Current quantitative gene expression detection in genomic and transcriptomic research heavily relies on quantitative real-time PCR (qPCR). While existing multiplex gene detection techniques offer simultaneous analysis of multiple targets, we present an alternative assay capable of detecting gene expression simultaneously within a single well. This highly sensitive method utilizes πCode MicroDiscs, featuring unique identification patterns and fluorescent detection. Our study compared this multiplex πCode platform with a qPCR platform for profiling cytokine gene expression. The πCode MicroDisc assay successfully demonstrated the expression of polymerization markers for M1- and M2-like macrophages generated from THP-1-derived macrophages in a qualitative assay. Additionally, our findings suggest a pattern agreement between the πCode assay and the qPCR assay, indicating the potential of the πCode technology for comparative gene expression analysis. Regarding the inherent sensitivity and linearity, the developed πCode assay primarily provides qualitative gene expression to discriminate the polarization of macrophages. This remarkable capability presents substantial advantages for researchers, rendering the technology highly suitable for high-throughput applications in clinical diagnosis and disease monitoring.
Topics: Humans; Cytokines; Macrophages; Biosensing Techniques; Photons; Gene Expression Profiling; Gene Expression; Real-Time Polymerase Chain Reaction
PubMed: 38920610
DOI: 10.3390/bios14060306 -
Frontiers in Immunology 2024Vascular calcification (VC) is considered a common pathological process in various vascular diseases. Accumulating studies have confirmed that VC is involved in the... (Review)
Review
Vascular calcification (VC) is considered a common pathological process in various vascular diseases. Accumulating studies have confirmed that VC is involved in the inflammatory response in heart disease, and SPP1+ macrophages play an important role in this process. In VC, studies have focused on the physiological and pathological functions of macrophages, such as pro-inflammatory or anti-inflammatory cytokines and pro-fibrotic vesicles. Additionally, macrophages and activated lymphocytes highly express SPP1 in atherosclerotic plaques, which promote the formation of fatty streaks and plaque development, and SPP1 is also involved in the calcification process of atherosclerotic plaques that results in heart failure, but the crosstalk between SPP1-mediated immune cells and VC has not been adequately addressed. In this review, we summarize the regulatory effect of SPP1 on VC in T cells, macrophages, and dendritic cells in different organs' VC, which could be a potential therapeutic target for VC.
Topics: Humans; Osteopontin; Vascular Calcification; Animals; Macrophages; Dendritic Cells; T-Lymphocytes; Plaque, Atherosclerotic
PubMed: 38919629
DOI: 10.3389/fimmu.2024.1395596 -
Frontiers in Immunology 2024The transitory emergence of myeloid-derived suppressor cells (MDSCs) in infants is important for the homeostasis of the immune system in early life. The composition and...
The transitory emergence of myeloid-derived suppressor cells (MDSCs) in infants is important for the homeostasis of the immune system in early life. The composition and functional heterogeneity of MDSCs in newborns remain elusive, hampering the understanding of the importance of MDSCs in neonates. In this study, we unraveled the maturation trajectory of polymorphonuclear (PMN)-MDSCs from the peripheral blood of human newborns by performing single-cell RNA sequencing. Results indicated that neonatal PMN-MDSCs differentiated from self-renewal progenitors, antimicrobial PMN-MDSCs, and immunosuppressive PMN-MDSCs to late PMN-MDSCs with reduced antimicrobial capacity. We also established a simple framework to distinguish these distinct stages by CD177 and CXCR2. Importantly, preterm newborns displayed a reduced abundance of classical PMN-MDSCs but increased late PMN-MDSCs, consistent with their higher susceptibility to infections and inflammation. Furthermore, newborn PMN-MDSCs were distinct from those from cancer patients, which displayed minimum expression of genes about antimicrobial capacity. This study indicates that the heterogeneity of PMN-MDSCs is associated with the maturity of human newborns.
Topics: Humans; Myeloid-Derived Suppressor Cells; Infant, Newborn; Single-Cell Analysis; Receptors, Interleukin-8B; Gene Expression Profiling; Transcriptome; Neutrophils; GPI-Linked Proteins; Cell Differentiation; Female; Male; Isoantigens; Receptors, Cell Surface
PubMed: 38919617
DOI: 10.3389/fimmu.2024.1367230