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Frontiers in Immunology 2019TLR2 signaling plays a critical protective role against acute (Lm) infection by up-regulating inflammatory cytokines and promoting macrophage antimicrobial...
TLR2 signaling plays a critical protective role against acute (Lm) infection by up-regulating inflammatory cytokines and promoting macrophage antimicrobial capabilities. However, the underlying mechanism by which TLR2 regulates hepatic macrophage-mediated anti-Lm immune responses remains poorly understood. In this study, we found that both the absolute number and proportion of monocyte/macrophage (Mo/MΦ) in the liver and spleen of mice were significantly lower compared to wild type mice. Changes in TLR2 signaling in both hepatocytes and Mo/MΦs were associated with the infiltration of Mo/MΦs in response to Lm-infection. Analyses by proteome profiler array and ELISA revealed that hepatocytes recruited Mo/MΦs via TLR2-dependent secretion of CCL2 and CXCL1, which was confirmed by receptor blocking and exogenous chemokine administration. Importantly, we found that TLR2 contributed to macrophage mobility in the liver through a TLR2/NO/F-actin pathway, facilitating the formation of macrophage-associated hepatic microabscesses. Moreover, TLR2 activation induced the expression of several PRRs on hepatic macrophages associated with the recognition of Lm and augmented macrophage bacterial clearance activity. Our findings provide insight into the intrinsic mechanisms of TLR2-induced Mo/MΦ migration and mobility, as well as the interaction between macrophages and hepatocytes in resistance to Lm infection.
Topics: Animals; Listeria monocytogenes; Listeriosis; Liver; Liver Abscess; Macrophages; Mice; Mice, Knockout; Monocytes; Toll-Like Receptor 2
PubMed: 31297109
DOI: 10.3389/fimmu.2019.01388 -
PloS One 2015The aim of this study was to investigate histomorphological and immunophenotypic features in pill-induced esophagitis. We comparatively evaluated the histomorphological,... (Comparative Study)
Comparative Study
The aim of this study was to investigate histomorphological and immunophenotypic features in pill-induced esophagitis. We comparatively evaluated the histomorphological, immunophenotypic features of pill-induced esophagitis vs. reflux esophagitis, as well as clinical information and endoscopic findings. Fifty-two tissue pieces from 22 cases of pill-induced esophagitis, 46 pieces from 20 reflux esophagitis, and 16 pieces from 14 control samples were subjected to immunohistochemistry for inflammatory infiltrates (CD3 for T lymphocyte, CD20 for B lymphocyte, CD56 for NK cell, CD68 for macrophage, CD117 for mast cell) and eosinophil chemotaxis-associated proteins (Erk, leptin, leptin receptor, pSTAT3, phospho-mTOR). As a result, Histomorphology showed that a diffuse pattern of dilated intercellular spaces was more frequently observed in pill-induced esophagitis, while reactive atypia and subepithelial papillary elongation were more often found in reflux esophagitis (P < 0.05, respectively). Interestingly, intraepithelial eosinophilic microabscess, intraepithelial pustule and diffuse pattern of dilated intercellular spaces were observed in 14% (3 cases), 9% (2 cases) and 32% (7 cases) of pill-induced esophagitis, respectively, but in no cases of reflux esophagitis. Regarding intraepithelial inflammatory infiltrates in pill-induced esophagitis, T lymphocytes were the most common cells, followed by eosinophil; 11 and 7 in one x400 power field, respectively. Intraepithelial pSTAT3-positive pattern was more frequently observed in pill-induced esophagitis than in reflux esophagitis, at 45% (10 cases) versus 10% (2 cases), respectively (P < 0.05). Considering the distal esophageal lesion only, intraepithelial pustule, diffuse dilated intercellular spaces and stromal macrophages were more frequently found in distal pill-induced esophagitis, whereas reactive atypia and intraepithelial mast cells in reflux esophagitis (P < 0.05, respectively). In conclusion, diffuse dilated intercellular spaces, intraepithelial eosinophil microabscess, pustule, T lymphocytes, eosinophils, and pSTAT3 positivity can be added to histopathological features of pill-induced esophagitis, other than non-specific ulcer. Besides, distal pill-induced esophagitis may be histopathologically differentiated from reflux esophagitis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD; B-Lymphocytes; Esophagitis; Esophagus; Female; Gastroesophageal Reflux; Humans; Immunohistochemistry; Immunophenotyping; Killer Cells, Natural; Male; Middle Aged; T-Lymphocytes; Young Adult
PubMed: 26047496
DOI: 10.1371/journal.pone.0128110 -
Clinical Epigenetics Mar 2022Psoriasis is a chronic and hyperproliferative skin disease featured by hyperkeratosis with parakeratosis, Munro micro-abscess, elongation of rete pegs, granulosa...
BACKGROUND
Psoriasis is a chronic and hyperproliferative skin disease featured by hyperkeratosis with parakeratosis, Munro micro-abscess, elongation of rete pegs, granulosa thinning, and lymphocyte infiltration. We previously profiled gene expression and chromatin accessibility of psoriatic skins by transcriptome sequencing and ATAC-seq. However, integrating both of these datasets to unravel gene expression regulation is lacking. Here, we integrated transcriptome and ATAC-seq of the same psoriatic and normal skin tissues, trying to leverage the potential role of chromatin accessibility and their function in histopathology features.
RESULTS
By inducing binding and expression target analysis (BETA) algorithms, we explored the target prediction of transcription factors binding in 15 psoriatic and 19 control skins. BETA identified 408 upregulated genes (rank product < 0.01) and 133 downregulated genes linked with chromatin accessibility. We noticed that cumulative fraction of genes in upregulation group was statistically higher than background, while that of genes in downregulation group was not significant. KEGG pathway analysis showed that the upregulated 408 genes were enriched in TNF, NOD, and IL-17 signaling pathways. In addition, the motif module in BETA suggested the 57 upregulated genes are targeted by transcription factor AP-1, indicating that increased chromatin accessibility facilitated the binding of AP-1 to the target regions and further induced expression of relevant genes. Among these genes, SQLE, STRN, EIF4, and MYO1B expression was increased in patients with hyperkeratosis, parakeratosis, and acanthosis thickening.
CONCLUSIONS
In summary, with the advantage of BETA, we identified a series of genes that contribute to the disease pathogenesis, especially in modulating histopathology features, providing us with new clues in treating psoriasis.
Topics: Chromatin; DNA Methylation; Humans; Parakeratosis; Psoriasis; Transcription Factor AP-1; Transcriptome
PubMed: 35277199
DOI: 10.1186/s13148-022-01250-6 -
Cureus May 2020Tuberculosis (TB) is a major public health problem in developing countries. It can affect any organ of the body, and can have a multitude of clinical presentations. We...
Tuberculosis (TB) is a major public health problem in developing countries. It can affect any organ of the body, and can have a multitude of clinical presentations. We present the case of a 22-year-old male who presented with fever, abdominal pain, and weight loss, and was found to have enlarged liver and spleen, both studded with multiple microabscesses. He had deranged liver functions, mild anemia, and elevated acute phase reactants. Examination of the aspirate from the liver did not reveal any organism on microscopy or culture. Based on the demographics, history of contact with a TB patient, positive Mantoux test, and clinical and radiological features, the patient was successfully managed with empirical treatment for TB.
PubMed: 32596067
DOI: 10.7759/cureus.8247 -
Annals of Clinical and Laboratory... Sep 2022Tuberculosis (TB) and SARS-CoV-2 (COVID-19) are two important infectious diseases causing morbidity and mortality worldwide. Active TB infection can stimulate host...
Tuberculosis (TB) and SARS-CoV-2 (COVID-19) are two important infectious diseases causing morbidity and mortality worldwide. Active TB infection can stimulate host immune responses and together with COVID-19, may lead to cytokine storm and immune dysregulation leading to multi-organ failure. We present a rare case of both miliary tuberculosis and SARS-CoV-2 co-infection in an infant who was a 6-month-old previously healthy term boy. He had persistent cough and congestion, became severely ill, and was brought to the emergency department. He was found to be COVID-19 positive by PCR test. Laboratory studies showed pancytopenia, elevated inflammatory markers, and an abnormal coagulation profile with coagulopathy. He developed strokes, severe sepsis, and electrolyte abnormalities, and declined rapidly within 6 days. Autopsy examination showed multifocal micro-abscesses in multiple organs, which on microscopic examination showed necrotic foci teeming with Mycobacteria and were culture positive for Neuropathological examination showed infarction in the right middle and posterior cerebral artery territories. This patient helps illuminate some immunological and pathological aspects of two co-occurring infectious diseases and the susceptibility for the development of fatal complications with SARS-CoV-2 infection in the pediatric population.
Topics: Child; Male; Humans; Infant; Tuberculosis, Miliary; COVID-19; SARS-CoV-2; Mycobacterium tuberculosis; Electrolytes
PubMed: 36261183
DOI: No ID Found -
BJR Case Reports Mar 2020is the third most frequent cause of bacterial meningitis and has a predilection for elderly patients and the immunosuppressed. A small number of patients with...
is the third most frequent cause of bacterial meningitis and has a predilection for elderly patients and the immunosuppressed. A small number of patients with meningoencephalitis have previously been reported to experience stroke-like symptoms that were attributed to microabscess formation and the mass effect of collections of infection in the brain. These infections led to temporary neurological deficits that resolved with antimicrobial treatment, rather than to true strokes with permanent neurological deficits. This report discusses the case of an 80- year-old male, who was immunosuppressed with mesalazine for the treatment of Crohn's disease, and who went on to develop meningoencephalitis. 1 week into his admission, for antibiotic therapy, the patient began to experience new onset right upper limb weakness, nystagmus and past pointing. These symptoms were initially thought to be a complication of the infection. However, subsequent diffusion-weighted MRI revealed that the patient had more likely suffered an acute ischaemic event and a contrast-enhanced MRI performed later could not detect any abscess or large infective focus in a region that could explain the symptoms. This case report highlights the fact that ischaemic and infective pathologists may coexist in immunosuppressed Listeria patients and that clinical signs and symptoms should guide the use of appropriate imaging modalities such as MRI to clarify differentials so that ischaemia is not mistaken for the more common stroke mimic caused by infection in these patients.
PubMed: 32201611
DOI: 10.1259/bjrcr.20190068 -
Respiratory Physiology & Neurobiology Mar 2023Coronavirus disease-2019 (COVID-19) may severely affect respiratory function and evolve to life-threatening hypoxia. The clinical experience led to the implementation of... (Review)
Review
Coronavirus disease-2019 (COVID-19) may severely affect respiratory function and evolve to life-threatening hypoxia. The clinical experience led to the implementation of standardized protocols assuming similarity to severe acute respiratory syndrome (SARS-CoV-2). Understanding the histopathological and functional patterns is essential to better understand the pathophysiology of COVID-19 and then develop new therapeutic strategies. Epithelial and endothelial cell damage can result from the virus attack, thus leading to immune-mediated response. Pulmonary histopathological findings show the presence of Mallory bodies, alveolar coating cells with nuclear atypia, reactive pneumocytes, reparative fibrosis, intra-alveolar hemorrhage, moderate inflammatory infiltrates, micro-abscesses, microthrombus, hyaline membrane fragments, and emphysema-like lung areas. COVID-19 patients may present different respiratory stages from silent to critical hypoxemia, are associated with the degree of pulmonary parenchymal involvement, thus yielding alteration of ventilation and perfusion relationships. This review aims to: discuss the morphological (histopathological and radiological) and functional findings of COVID-19 compared to acute interstitial pneumonia, acute respiratory distress syndrome (ARDS), and high-altitude pulmonary edema (HAPE), four entities that share common clinical traits, but have peculiar pathophysiological features with potential implications to their clinical management.
Topics: Humans; COVID-19; SARS-CoV-2; Altitude; Pulmonary Edema; Pneumonia; Respiratory Distress Syndrome
PubMed: 36460252
DOI: 10.1016/j.resp.2022.104000 -
Human Pathology Jan 2023Chemoradiation-associated injury may cause marked epithelial and stromal changes in gastric specimens. We characterized these histologic features in a retrospective...
Chemoradiation-associated injury may cause marked epithelial and stromal changes in gastric specimens. We characterized these histologic features in a retrospective series of cases. Nineteen cases of radiochemotherapy-associated gastropathy were identified, including 16 from our institution and 3 from consultation material. Patient charts and hematoxylin and eosin-stained slides were reviewed. Most patients were men (79%) with a median age of 66 years. All patients had a documented history of radiation and 15 patients also received chemotherapy. The median time from treatment to biopsy or resection was 2.3 months. Gross and endoscopic findings included erythematous, hemorrhagic, or ulcerated mucosa. Mucosal eosinophilia was seen in 16 cases (84%) while 10 cases (53%) featured acute inflammation including neutrophilic microabscesses. Epithelial changes included increased apoptosis (6 cases, 32%) and marked epithelial atypia (10 cases, 53%), potentially mimicking malignancy in some cases. However, the atypical cells featured voluminous eosinophilic cytoplasm with low nuclear-to-cytoplasmic ratio, a clue to their benign nature. Neuroendocrine cell nests were seen in 4 cases (21%) and loosely aggregated in 1 case, potentially mimicking a well-differentiated neuroendocrine tumor or enterochromaffin-like (ECL) cell hyperplasia in autoimmune gastritis. Eleven cases (58%) featured vascular changes that included vessel dilation, hobnailed endothelial cells, and fibrin thrombi. Stromal changes were seen in 11 cases (58%) and included lamina propria hyalinization, submucosal fibrosis, and myofibroblast atypia. Injury associated with radiochemotherapy is histologically varied and may affect epithelial, stromal, and vascular compartments. Familiarity with these features is important as a subset of these findings may provoke concern for neoplasia.
Topics: Male; Humans; Aged; Female; Retrospective Studies; Endothelial Cells; Esophagogastric Junction; Gastritis; Biopsy
PubMed: 36495943
DOI: 10.1016/j.humpath.2022.12.002 -
Dermatopathology (Basel, Switzerland) May 2022Pemphigus is a chronic blistering disorder caused by autoantibodies that target desmosomal proteins in the epidermis. Acantholysis may be absent, and pemphigus may...
Pemphigus is a chronic blistering disorder caused by autoantibodies that target desmosomal proteins in the epidermis. Acantholysis may be absent, and pemphigus may present only with spongiosis and vesiculation, thereby leading to a misdiagnosis of eczema. Herein, we conducted a retrospective, observational, single-center study to establish a pattern of spongiosis in cases of pemphigus confirmed by direct immunofluorescence. Immunopathologically diagnosed pemphigus specimens from 2001 to 2020 were retrieved, and specimens with spongiosis were analyzed for the following features: vesiculation, acantholysis, spongiosis, inflammatory cells in the epidermis, and inflammation in the dermis. Cases of spongiotic dermatitis were used as control. Out of 99 immunopathologically diagnosed pemphigus specimens, 41 samples with spongiosis were identified. About one quarter of the specimens did not have acantholysis. Spongiosis in the middle to lower thirds of the perilesional epidermis (p = 0.030), exocytosis with either neutrophils or eosinophils (p = 0.016), dermal infiltrates composed of lymphocytes, eosinophils, and neutrophils (p = 0.012), and absence of Langerhans cell microabscesses (p < 0.001) were more common in pemphigus than control. Spongiosis in pemphigus may mimic eczema in patients without acantholysis. The subtle histological findings in this study provide diagnostic clues and suggest that further immunofluorescence should be performed to confirm pemphigus diagnosis.
PubMed: 35645233
DOI: 10.3390/dermatopathology9020022 -
Oncology Letters Jan 2020Granulomatous lobular mastitis (GLM) and mammary duct ectasia (MDE) are inflammatory diseases. However, only a limited number of studies have focused on characterizing...
Granulomatous lobular mastitis (GLM) and mammary duct ectasia (MDE) are inflammatory diseases. However, only a limited number of studies have focused on characterizing their clinicopathological features. The aim of the present study was to investigate the etiology, clinicopathological characteristics and diagnosis of GLM and MDE. The clinical information and treatment of 118 female patients with pathologically-proven GLM or MDE were retrospectively analyzed in the present study. A total of 29 cases had GLM, 77 had MDE and 12 had GLM accompanied by MDE. GLM tends to occur in patients who have had their last birth within 5 years and are usually <40 years of age. GLM masses were usually larger than MDE masses and suppurated or ulcerated more easily. Histopathologically, GLM was characterized by a significant granulomatous inflammatory reaction centered on lobules. Compared with MDE, GLM had a higher incidence of granuloma and microabscess formation within the lobules and surrounding tissue. More multinucleated giant cells within granuloma were observed in patients with GLM than in those with MDE, while MDE was characterized by significant dilatation of the duct terminals and inflammatory changes in the duct wall and periductal tissues. When compared with patients with GLM, foam cells within the duct epithelium or surrounding stroma were more common in patients with MDE. The present study demonstrated that GLM and MDE had distinct clinicopathological characteristics. Further research is required in order to identify more appropriate treatment strategies for these specific types of breast inflammation.
PubMed: 31885718
DOI: 10.3892/ol.2019.11156