Sporotrichosis: Review of Innate and Acquired Immune Mechanisms

Context: Different factors such as the site of infection, the etiological agent, and the immune system can modify the antifungal response of the host. Differences in Sporothrix schenckii strains’ virulence and the host’s immune competency may be involved in the development of sporotrichosis. Nevertheless, the mechanisms related to the disease’s development and progression remain not fully elucidated. Nowadays, no model outweighs the usefulness of mice in biological studies. In these models, transient controlled immunity is created by depressed inflammatory cells during the acute phase of the disease. This is also related to nitric oxide-induced T-cell apoptosis and the lack of a mitogen response. Evidence Acquisition: The recognition of the lipid components of S. schenckii can induce and prolong inflammation. This recognition occurs mainly through the Toll-like receptor (TLR)-4 or the inflammasome. At the same time, TLR-2-mediated identification of fungal exoantigen can serve as an immune evasion process, continuing and worsening the infection. Cell-mediated immune mechanisms have a predominant influence on modulating the clinical expression of sporotrichosis, which is mainly related to Th1/Th17 immunity. Conclusions: In this study, we aimed to explore the innate and acquired immune mechanisms involved in sporotrichosis, as well as the most commonly used animal models for experimental studies.

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Multilayered stable 2D nano-sheets of Ti2NTx MXene: synthesis, characterization, and anticancer activity

Journal of Nanobiotechnology ◽

10.1186/s12951-019-0545-4 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 10

Author(s):

A. Szuplewska ◽

A. Rozmysłowska-Wojciechowska ◽

S. Poźniak ◽

T. Wojciechowski ◽

M. Birowska ◽

...

Keyword(s):

Biological Activity ◽

Mammary Epithelial Cells ◽

Theoretical Calculations ◽

Experimental Studies ◽

Reactive Oxygen ◽

Decisive Role ◽

Max Phase ◽

Mechanisms Of Toxicity ◽

Biological Studies

Abstract Background The biological activity of MXenes has been studied for several years because of their potential biomedical applications; however, investigations have so far been limited to 2D titanium carbides. Although monolayered Ti2NTx MXene has been expected to have biological activity, experimental studies revealed significant difficulties due to obstacles to its synthesis, its low stability and its susceptibility to oxidation and decomposition. Results In this paper, we report our theoretical calculations showing the higher likelihood of forming multilayered Ti2NTx structures during the preparation process in comparison to single-layered structures. As a result of our experimental work, we successfully synthesized multilayered Ti2NTx MXene that was suitable for biological studies by the etching of the Ti2AlN MAX phase and further delamination. The biocompatibility of Ti2NTx MXene was evaluated in vitro towards human skin malignant melanoma cells, human immortalized keratinocytes, human breast cancer cells, and normal human mammary epithelial cells. Additionally, the potential mode of action of 2D Ti2NTx was investigated using reactive oxygen tests as well as SEM observations. Our results indicated that multilayered 2D sheets of Ti2NTx showed higher toxicity towards cancerous cell lines in comparison to normal ones. The decrease in cell viabilities was dose-dependent. The generation of reactive oxygen species as well as the internalization of the 2D sheets play a decisive role in the mechanisms of toxicity. Conclusions We have shown that 2D Ti2NTx in the form of multilayered nanoflakes exhibits fair stability and can be used for in vitro studies. These results show promise for its future applications in biotechnology and nanomedicine.

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Increased Expressions of Toll-Like Receptor 4 on Platelet Are Related to Type of Bacteria and Disease Severity in Patients with Sepsis

Blood ◽

10.1182/blood.v112.11.5365.5365 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5365-5365

Author(s):

Liping Ma ◽

Xiu-Ju Wang ◽

Da-Nian Nie ◽

Yi-Qing Li ◽

Shuang-Fen Xie ◽

...

Keyword(s):

Blood Platelets ◽

Inflammatory Cells ◽

Gram Negative Bacteria ◽

Toll Like Receptor ◽

Microbial Infection ◽

Toll Like Receptor 4 ◽

Gram Positive ◽

Severe Problem ◽

Gram Negative ◽

Gram Positive Bacteria

Abstract Early diagnosis and treatment of patients with sepsis remain a common and severe problem, especially in leukopenic patients.. Toll-like receptor-4 (TLR4) plays a crucial role in immunity as the first defenses system against microbial infection through binding gram-negative bacterial LPS. Blood platelets are not only involved in hemostasis, they also have many features of classic inflammatory cells. The expression of TLR4 on platelet in patients with sepsis, including gram-positive bacteria and gram-negative bacteria, is not known. Studying the differences between them, we investigated whether the expressions of TLR4 on platelet were associated with platelet activation, serum TNF-a and endotoxin levels in patients with sepsis, 8 patients of them with gram-positive bacteria and 15 patients of them with gram-negative bacteria. The number of platelet and function of coagulation were normal before infecting. Comparing with the heath subjects, the expressions of TLR4 and P-selectin on platelets, the levels of serum TNF-a and endotoxin were higher (P<0.05),and there was a positive correlation was observed between TLR4 and P-selectin, TNF-a, endotoxin respectively, among the gram-negative bacterial subjects. The phenomena were not found among the gram-positive bacterial subjects. In addition, among the gram-negative bacterial subjects, the expression of TLR4 was higher in patients with decreased number of platelets than with normal number of platelets. These results suggest that increased TLR4 on platelet might be an important early sign of gram-negative bacteria in patient with sepsis, it contributes to platelet activating, the inflammatory process and disease activity in infecting host. Above has be doing in more patients with positive blood bacteria culture in our Lab.

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Cobalt ions recruit inflammatory cells in vitro through human Toll-like receptor 4

Biochemistry and Biophysics Reports ◽

10.1016/j.bbrep.2016.07.003 ◽

2016 ◽

Vol 7 ◽

pp. 374-378 ◽

Cited By ~ 4

Author(s):

Helen Lawrence ◽

David J. Deehan ◽

James P. Holland ◽

Sami A. Anjum ◽

Amy E. Mawdesley ◽

...

Keyword(s):

Inflammatory Cells ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Cobalt Ions

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TLR4 (Toll-Like Receptor 4) Mediates the Development of Intracranial Aneurysm Rupture

Hypertension ◽

10.1161/hypertensionaha.118.12595 ◽

2020 ◽

Vol 75 (2) ◽

pp. 468-476

Author(s):

Kazuha Mitsui ◽

Taichi Ikedo ◽

Yoshinobu Kamio ◽

Hajime Furukawa ◽

Michael T. Lawton ◽

...

Keyword(s):

Intracranial Aneurysm ◽

Knockout Mice ◽

Critical Factor ◽

Inflammatory Cells ◽

Aneurysm Rupture ◽

Primary Response ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Aneurysmal Rupture ◽

Rupture Rate

Inflammation is emerging as a critical factor in the pathophysiology of intracranial aneurysm. TLR4 (toll-like receptor 4) contributes not only to the innate immune responses but also to the inflammatory processes associated with vascular disease. Therefore, we examined the contribution of the TLR4 pathway to the development of the rupture of intracranial aneurysm. We used a mouse model of intracranial aneurysm. TLR4 inhibition significantly reduced the development of aneurysmal rupture. In addition, the rupture rate and levels of proinflammatory cytokines were lower in TLR4 knockout mice than the control littermates. Macrophage/monocyte-specific TLR4 knockout mice had a lower rupture rate than the control littermate mice. Moreover, the deficiency of MyD88 (myeloid differentiation primary-response protein 88), a key mediator of TLR4, reduced the rupture rate. These findings suggest that the TLR4 pathway promotes the development of intracranial aneurysmal rupture by accelerating inflammation in aneurysmal walls. Inhibition of the TLR4 pathway in inflammatory cells may be a promising approach for the prevention of aneurysmal rupture and subsequent subarachnoid hemorrhage.

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Cardiac Lymphatic Dysfunction Causes Drug-Eluting Stent–Induced Coronary Hyperconstricting Responses in Pigs In Vivo

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.119.312396 ◽

2019 ◽

Vol 39 (4) ◽

pp. 741-753 ◽

Cited By ~ 3

Author(s):

Hirokazu Amamizu ◽

Yasuharu Matsumoto ◽

Susumu Morosawa ◽

Kazuma Ohyama ◽

Hironori Uzuka ◽

...

Keyword(s):

Experimental Studies ◽

Lymphatic Vessels ◽

Rho Kinase ◽

Inflammatory Cells ◽

Bare Metal Stent ◽

Drug Eluting Stent ◽

Kinase Activation ◽

Coronary Vasomotion ◽

Drug Eluting

Objective— We have previously demonstrated that coronary adventitial inflammation plays important roles in the pathogenesis of coronary vasomotion abnormalities, including drug-eluting stent (DES)–induced coronary hyperconstricting responses. Importantly, the adventitia also harbors lymphatic vessels, which may prevent inflammation by transporting extravasated fluid and inflammatory cells. We thus aimed to examine the roles of coronary adventitial lymphatic vessels in the pathogenesis of DES-induced coronary hyperconstricting responses in a porcine model in vivo. Approach and Results— We performed 2 experimental studies. In protocol 1, 15 pigs were divided into 3 groups with or without DES and with bare metal stent. Nonstented sites 20 mm apart from stent implantation also were examined. In the protocol 2, 12 pigs were divided into 2 groups with or without lymphatic vessels ligation followed by DES implantation at 2 weeks later (n=6 each). We performed coronary angiography 4 weeks after DES implantation, followed by immunohistological analysis. In protocol 1, the number and the caliber of lymphatic vessels were greater at only the DES edges after 4 more weeks. In protocol 2, coronary hyperconstricting responses were further enhanced in the lymphatic vessels ligation group associated with adventitial inflammation, Rho-kinase activation, and less adventitial lymphatic vessels formation. Importantly, there were significant correlations among these inflammation-related changes and enhanced coronary vasoconstricting responses. Conclusions— These results provide evidence that cardiac lymphatic vessel dysfunction plays important roles in the pathogenesis of coronary vasoconstrictive responses in pigs in vivo.

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Inhibitions of HMGB1 and TLR4 alleviate DINP-induced asthma in mice

Toxicology Research ◽

10.1039/c9tx00048h ◽

2019 ◽

Vol 8 (5) ◽

pp. 621-629 ◽

Cited By ~ 4

Author(s):

Yun-Ho Hwang ◽

Yongjin Lee ◽

Man-Jeong Paik ◽

Sung-Tae Yee

Keyword(s):

Airway Hyperresponsiveness ◽

High Mobility ◽

Inflammatory Cells ◽

The Other ◽

Chromosomal Protein ◽

Toll Like Receptor ◽

Mucus Production ◽

Tlr4 Signaling ◽

Cytokine Levels ◽

Signaling Inhibitors

Abstract We studied the effects of high mobility group box chromosomal protein 1 (HMGB1) and toll-like receptor (TLR4) in diisonoyl phthalate (DINP)-induced asthma. Mice with DINP-induced asthma were treated with a TLR4-signaling inhibitor or anti-HMGB1 antibody, and various markers of asthma were measured 24 h later. DINP increased airway hyperresponsiveness, numbers of cells in BALF, numbers of inflammatory cells (leukocytes, lymphocytes, monocytes, eosinophils, neutrophils, basophils) in blood, mucus production, pulmonary fibrosis, Th2 type cytokine levels in BALF, and lung cell apoptosis. On the other hand, administrations of TLR4-signaling inhibitors (TAK-242) or anti-HMGB1 antibodies to a mouse model of DINP-induced asthma reduced biological markers of asthma. These results show TLR4 and HMGB1 both contribute to DINP-induced asthma, and that the inhibitions of TLR4 or HMGB1 offer potential means of treating asthma induced by phthalates like DINP.

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EXPERIMENTAL SURVIVAL STUDIES OF SPOROTHRIX SCHENCKII IN A MEAT PRODUCT1

Journal of Milk and Food Technology ◽

10.4315/0022-2747-36.6.311 ◽

1973 ◽

Vol 36 (6) ◽

pp. 311-314 ◽

Cited By ~ 1

Author(s):

J. H. Scharding ◽

D. C. Kelley ◽

J. E. Cook ◽

D. H. Kropf

Keyword(s):

High Temperatures ◽

Health Hazard ◽

Experimental Studies ◽

Sporothrix Schenckii ◽

Test Model ◽

Potential Health ◽

Cooking Process ◽

Potential Health Hazard ◽

Survival Studies

The literature includes a few reports on the ability of the fungus Sporothrix schenckii to survive at high temperatures, and one suggests that it could survive processing procedures used to manufacture frankfurters. Reported are studies to determine the extent that S. schenckii could survive processing procedures used by most manufacturers of commercial frankfurters. A frankfurter test model was devised to approximate the length diameter, and cooking characteristics of a commercial frankfurter. Uncooked emulsion was inoculated with the organism and recovery was attempted throughout the experimental cooking process. In 32% of the experimental studies, the maximum times and temperatures for positive recovery of the organism met or exceeded the processing standards used by most manufacturers. Thus, S. schenckii may survive in commercial frankfurters and be a potential health hazard.

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Anti-TNF-α Treatment and Bile Duct Drainage Restore Cellular Immunity and Prevent Tissue Injury in Experimental Obstructive Jaundice

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463200702000425 ◽

2007 ◽

Vol 20 (4) ◽

pp. 855-860 ◽

Cited By ~ 14

Author(s):

F.J. Padillo ◽

A. Cruz ◽

I. Segura-Jiménez ◽

J. Ruiz-Rabelo ◽

M.R. Vázquez-Ezquerra ◽

...

Keyword(s):

Bile Duct ◽

Liver Injury ◽

Obstructive Jaundice ◽

Renal Insufficiency ◽

Tissue Injury ◽

Experimental Studies ◽

Inflammatory Cells ◽

Activation Markers ◽

Tnf Α ◽

The Impact

Several experimental studies of obstructive jaundice (OJ) have shown the presence of immunosuppressive state associated with the rise of tumor necrosis factor-α (TNF-α) concentration in plasma. The present study evaluates the impact of anti-TNF-α administration or bile duct drainage on the inflammatory response, liver injury and renal insufficiency in obstructed rats. OJ was induced by the ligation of bile duct in Wistar rats. The parameters were determined at 14 and 21 days after OJ. Two additional groups of animals were treated with anti-TNF-α antibodies or submitted to bile duct drainage at 14 days, and sacrificed 21 days after OJ. Cholestasis decreased glucose, and enhanced urea, Creatinin, bilirubin and transaminases. Cholestasis increased the number of different inflammatory cells (T and B lymphocytes, and monocytes-macrophages) but reduced the expression of the corresponding cellular activation markers. This low responsiveness of the inflammatory cells was related to a decreased free radical production and phagocytic activity of cells. Anti-TNF-α and bile duct drainage reduced tissue injury, and prevented the reduction of the number and activity of T lymphocytes and phagocytic cells observed at the advanced stages of cholestasis. In conclusion, anti-TNF-α and bile duct drainage improved cell immunodeficiency, and reduced liver injury, cholestasis and renal insufficiency in experimental OJ.

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The current analysis of the effect of hyperbaric oxygen therapy on the frostbitten tissue: Experimental study in rabbits

Open Medicine ◽

10.2478/s11536-008-0054-6 ◽

2009 ◽

Vol 4 (2) ◽

pp. 198-202 ◽

Cited By ~ 2

Author(s):

Fatih Uygur ◽

Nurettin Noyan ◽

Celalettin Sever ◽

Tuna Gümüş

Keyword(s):

Mast Cells ◽

Hyperbaric Oxygen ◽

Hyperbaric Oxygen Therapy ◽

Inflammatory Process ◽

Oxygen Therapy ◽

Experimental Studies ◽

Thromboxane A2 ◽

Inflammatory Cells ◽

Current Analysis ◽

Prostaglandin I2

AbstractMany experimental studies have been performed and the mechanism of hyperbaric oxygen therapy on the frostbitten tissue has not been elucidated. In this study, we evaluated the effect of hyperbaric oxygen therapy on the frostbitten ears of rabbits in an experimental animal model by examining the concentrations of thromboxane A2 (as thromboxane B2-Tx B2) and of prostaglandin I2 (PG I2) (as 6-keto-prostaglandin F1α-PG F1α) in tissues, and by counting the numbers of inflammatory cells (neutrophils and mast cells-MC) Hyperbaric oxygen therapy (HBO) at 2.5 ATA for 90 minutes twice daily for fourteen days to rabbits, the ears of which were subjected to frostbite, decreased presence of inflammatory cells (mast cells −75%; neutrophils −40%) and increased prostaglandin I2 (PG I2) (as 6-Keto-PGF1α) in the involved skin. Thromboxane A2 (TxA2) (as Tx B2) was unaffected. Our results revealed that an inflammatory process was the underlying cause of frostbite injury and that hyperbaric oxygen therapy was active in pathological situations involving an inflammatory process in frostbite.

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