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Kenta Fujimoto, Takehiro Motowaki, Naoya Tamura, Yasuaki Aratani
Myeloperoxidase (MPO), a major component of neutrophils, catalyzes the production of hypochlorous acid from hydrogen peroxide and chloride anion. Phagocytosis is a critical event induced by neutrophils for host defense and inflammation. Interestingly, we found that MPO-deficient (MPO(-/-)) neutrophils engulfed larger amounts of zymosan than wild-type neutrophils. Blocking of the CD11b subunit of complement receptor 3 (CR3) as well as inhibition of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) dramatically reduced zymosan phagocytosis...
October 4, 2016: Free Radical Research
Hongkun Bao, Lijuan Sun, Ying Zhu, Pengzhan Ran, Weihong Hu, Keming Zhu, Bai Li, Yangyang Hou, Jun Nie, Tangxin Gao, Liping Shan, Kai Du, Shangyong Zheng, Bingrong Zheng, Chunjie Xiao, Jing Du
Lentinan (LNT) is an immune regulator and its potential and mechanism for the treatment of mood disorder is of our interest. Dectin-1 is a β-glucan (including LNT) receptor that regulates immune functions in many immune cell types. Cumulative evidence has suggested that the glutamatergic system seems to play an important role in the treatment of depression. Here, we studied the antidepressant-like effects of LNT and its therapeutical target in regulating the functions of AMPA receptors. We found that 60min treatment with LNT leads to a significant antidepressant-like effect in the tail suspension test (TST) and the forced swim test (FST) in mice...
September 28, 2016: Behavioural Brain Research
Sanja Stopinšek, Alojz Ihan, Barbara Salobir, Marjeta Terčelj, Saša Simčič
BACKGROUND: Composition of organic dust is very complex, involving particles of microbial, animal and plant origin. Several environmental exposure studies associate microbial cell wall agents in organic dust with various respiratory symptoms and diseases. The aim of the present study was to investigate the in vitro effects of the co-exposure of fungal cell wall agents (FCWAs) and bacterial lipopolysaccharide (LPS) on inflammatory immune responses of peripheral blood mononuclear cells (PBMCs) from patients with pulmonary sarcoidosis...
2016: Journal of Occupational Medicine and Toxicology
Uzma Malik, Aneela Javed
Mammalian immune system is a complex amalgam of diverse cellular and noncellular components such as cytokines, receptors and co-receptors. FAM26F (family with sequence similarity 26, member F) is a recently identified tetraspanin-like membrane glycoprotein which is predicted to make homophilic interactions and potential synapses between several immune cells including CD4(+), CD8(+), NK, dendritic cells and macrophages. Various whole transcriptome analyses have demonstrated the differential expression of FAM26F in several bacterial, viral and parasitic infections, in certain pathophysiological conditions such as liver and heart transplantation, and in various cancers...
September 19, 2016: International Reviews of Immunology
Kerstin A Heyl, Christian M Karsten, Hortense Slevogt
Changes in the glycosylation of immunoglobulins have been shown to modulate immune homeostasis and disease pathology. In this sense it has been shown that highly galactosylated but not agalactosylated IgG1 immune complexes (ICs) inhibit C5aR-mediated pro-inflammatory immune responses via the assembly of FcγRIIB-Dectin-1 receptor complexes. In this study we demonstrated that Galectin-3, a galactose-binding lectin that is known to cross-link proteins on cell-surfaces via binding their N-glycans, bound to highly-galactosylated, but not agalactosylated IgG1...
October 7, 2016: Biochemical and Biophysical Research Communications
Yu Xia, Li Liu, Qi Bai, Jiajun Wang, Wei Xi, Yang Qu, Ying Xiong, Qilai Long, Jiejie Xu, Jianming Guo
Dectin-1, a classical pattern-recognition receptor, was now identified as an important regulator in immune homeostasis and cancer immunity through its extensive ligands binding functions and subsequent cytokines production. The aim of this study was to assess the clinical significance of dectin-1 expression in 290 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays. We found that dectin-1 was predominantly expressed on ccRCC cells, in accordance with several other online databases...
2016: Scientific Reports
John P Graham, Pierre Authie, Chun I Yu, Sandra M Zurawski, Xiao-Hua Li, Florentina Marches, Anne-Laure Flamar, Aditi Acharya, Jacques Banchereau, A Karolina Palucka
The targeting of vaccine antigens to antigen presenting cells (APC), such as dendritic cells (DCs), is a promising strategy for boosting vaccine immunogenicity and, in turn, protective and/or therapeutic efficacy. However, in vivo systems are needed to evaluate the potential of this approach for testing human vaccines. To this end, we examined human CD8(+) T-cell expansion to novel DC-targeting vaccines in vitro and in vivo in humanized mice. Vaccines incorporating the influenza matrix protein-1 (FluM1) antigen fused to human specific antibodies targeting different DC receptors, including DEC-205, DCIR, Dectin-1, and CD40, elicited human CD8(+) T-cell responses, as defined by the magnitude of specific CD8(+) T-cells to the targeted antigen...
September 22, 2016: Vaccine
Ken-Ichiro Minato, Lisa C Laan, Akihiro Ohara, Irma van Die
Many edible mushrooms have become attractive as "health foods" and as source materials for immunomodulators. To increase our insight in the immune-modulatory properties of a polysaccharide of the oyster mushroom Pleurotus citrinopileatus, PCPS, we analyzed its effects on the function of human dendritic cells (DCs). We showed that PCPS induces upregulation of the surface maturation markers CD80, CD86 and HLA-DR on DCs, indicating its potential to induce DC maturation. In addition, PCPS stimulates DCs to secrete the pro-inflammatory cytokines TNF, IL-1β, IL-6 and IL-12, as well as the anti-inflammatory cytokine IL-10, and induces enhanced mRNA levels of the chemokines CCL2, CCL3, CCL8, CXCL9, CXCL10, and LTA...
September 1, 2016: International Immunopharmacology
Beom-Seok Seo, Ha-Yan Park, Hee-Kyung Yoon, Yung-Choon Yoo, Junglim Lee, Seok-Rae Park
Heat-killed Saccharomyces cerevisiae (HKSC) is an agonist for Dectin-1, a major fungal cell wall β-glucan receptor. We previously reported that HKSC selectively enhances IgG1 production by LPS-activated mouse B cells. To determine if this IgG1 selectivity is caused by selective IgG1 class switching, we performed RT-PCRs for measuring germline transcripts (GLTs), flow cytometric analyses for detecting Ig-expressing cells, and ELISPOT assays for measuring the number of Ig-secreting cells in HKSC/LPS-stimulated mouse B cell cultures...
October 2016: Immunology Letters
Long Hang, Arthur M Blum, Sangeeta Kumar, Joseph F Urban, Makedonka Mitreva, Timothy G Geary, Armando Jardim, Mary M Stevenson, Clifford A Lowell, Joel V Weinstock
Helminthic infections modulate host immunity and may protect people in less-developed countries from developing immunological diseases. In a murine colitis model, the helminth Heligmosomoides polygyrus bakeri prevents colitis via induction of regulatory dendritic cells (DCs). The mechanism driving the development of these regulatory DCs is unexplored. There is decreased expression of the intracellular signaling pathway spleen tyrosine kinase (Syk) in intestinal DCs from H. polygyrus bakeri-infected mice. To explore the importance of this observation, it was shown that intestinal DCs from DC-specific Syk(-/-) mice were powerful inhibitors of murine colitis, suggesting that loss of Syk was sufficient to convert these cells into their regulatory phenotype...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Stephanie H Greco, Alejandro Torres-Hernandez, Aleksandr Kalabin, Clint Whiteman, Rae Rokosh, Sushma Ravirala, Atsuo Ochi, Johana Gutierrez, Muhammad Atif Salyana, Vishnu R Mani, Savitha V Nagaraj, Michael Deutsch, Lena Seifert, Donnele Daley, Rocky Barilla, Mautin Hundeyin, Yuriy Nikifrov, Karla Tejada, Bruce E Gelb, Steven C Katz, George Miller
Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle(-/-), and Dectin-1(-/-) mice...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Otavio Cabral-Marques, Rodrigo Nalio Ramos, Lena F Schimke, Taj Ali Khan, Eduardo Pinheiro Amaral, Caio César Barbosa Bomfim, Osvaldo Reis Junior, Tabata Takahashi França, Christina Arslanian, Joanna Darck Carola Correia Lima, Cristina Worm Weber, Janaíra Fernandes Ferreira, Fabiola Scancetti Tavares, Jing Sun, Maria Regina D Imperio Lima, Marília Seelaender, Vera Lucia Garcia Calich, José Alexandre Marzagão Barbuto, Beatriz Tavares Costa-Carvalho, Gabriela Riemekasten, Gisela Seminario, Liliana Bezrodnik, Luigi Notarangelo, Troy R Torgerson, Hans D Ochs, Antonio Condino-Neto
BACKGROUND: CD40 ligand (CD40L) deficiency predisposes to opportunistic infections, including those caused by fungi and intracellular bacteria. Studies of CD40L-deficient patients reveal the critical role of CD40L-CD40 interaction for the function of T-, B-, and dendritic cells. However, the consequences of CD40L deficiency on macrophage function remain to be investigated. OBJECTIVES: To determine the impact of CD40L absence on monocytes-derived macrophage (MDMs) responses...
August 20, 2016: Journal of Allergy and Clinical Immunology
Yinghua Zhao, Xiao Chu, Jintong Chen, Ying Wang, Sujun Gao, Yuxue Jiang, Xiaoqing Zhu, Guangyun Tan, Wenjie Zhao, Huanfa Yi, Honglin Xu, Xingzhe Ma, Yong Lu, Qing Yi, Siqing Wang
Dectin-1 signalling in dendritic cells (DCs) has an important role in triggering protective antifungal Th17 responses. However, whether dectin-1 directs DCs to prime antitumour Th9 cells remains unclear. Here, we show that DCs activated by dectin-1 agonists potently promote naive CD4(+) T cells to differentiate into Th9 cells. Abrogation of dectin-1 in DCs completely abolishes their Th9-polarizing capability in response to dectin-1 agonist curdlan. Notably, dectin-1 stimulation of DCs upregulates TNFSF15 and OX40L, which are essential for dectin-1-activated DC-induced Th9 cell priming...
2016: Nature Communications
A Pistiki, T Tsaganos, I Tsangaris, N Antonakos, G Damoraki, E J Giamarellos-Bourboulis
To study the differences of monocyte activation by albicans and non-albicans species of Candida and its change in sepsis, peripheral blood mononuclear cells were isolated from 17 healthy volunteers and 26 patients with severe sepsis/shock, and incubated in the absence/presence of heat-killed (HK) isolates of four different Candida species and purified β-D-glucan from C.albicans. Experiments were repeated in the presence and absence of inhibitors of intracellular activation pathways. Expression of annexin V on cells membranes of monocytes and lymphocytes, cytoplasmic activity of caspase-3, and DNA fragmentation of monocytes were studied...
November 2016: European Journal of Clinical Microbiology & Infectious Diseases
Emna Dabbeche-Bouricha, Luiza M Araujo, Masashi Kato, Armelle Prévost-Blondel, Henri-Jean Garchon
Mice transgenic for the RET oncogene provide a remarkable model for investigating the mechanisms underlying the promotion and the development of melanoma. This model was established on the C57BL/6 genetic background. In the present study, we investigated an effect of the strongly proinflammatory and autoimmune genetic makeup of the non-obese diabetic (NOD) strain. We bred (NODxB6)F1 mice and backcrossed them with NOD mice. F1 mice and mice at subsequent generations of backcrossing showed marked acceleration of tumor development, in particular with a more frequent and earlier extension of the primary uveal melanoma...
May 2016: Oncoimmunology
Hyung Sook Kim, Ki Hwan Park, Hong Kyung Lee, Ji Sung Kim, Yong Guk Kim, Jae Hee Lee, Ki Hun Kim, Jieun Yun, Bang Yeon Hwang, Jin Tae Hong, Youngsoo Kim, Sang-Bae Han
Curdlan, a β-1,3-glucan isolated from Alcaligenes faecalis, is an agonist of dectin-1 in various immune cells, including dendritic cells (DCs). However, whether curdlan also activates DCs through other receptors remains unknown. In this study, we found that curdlan activates DCs through dectin-1 and toll-like receptor 4 (TLR4). Curdlan increased the expression levels of surface molecules (CD40, CD80, CD86, and MHC-I/II), the production of cytokines (IL-12, IL-1β, TNF-α, and IFN-β), migration toward MIP-3β, and allogeneic T cell stimulation activity of DCs...
October 2016: International Immunopharmacology
Eui-Baek Byun, Beom-Su Jang, Eui-Hong Byun, Nak-Yun Sung
An effective method for activating macrophages and deriving a Th1 immune response could be used to improve the defenses of hosts. In this study, we investigated the immunomodulation effect and the related signaling mechanism of [Formula: see text]-(1,3)-glucan, isolated from the Agrobacterium species. Here, we found that [Formula: see text]-(1,3)-glucan predominantly induced the tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-1[Formula: see text], IL-6, IL-12p70, and nitric oxide, which was dependent on mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-[Formula: see text]B signaling...
2016: American Journal of Chinese Medicine
Gerald Wirnsberger, Florian Zwolanek, Tomoko Asaoka, Ivona Kozieradzki, Luigi Tortola, Reiner A Wimmer, Anoop Kavirayani, Friedrich Fresser, Gottfried Baier, Wallace Y Langdon, Fumiyo Ikeda, Karl Kuchler, Josef M Penninger
Fungal infections claim an estimated 1.5 million lives each year. Mechanisms that protect from fungal infections are still elusive. Recognition of fungal pathogens relies on C-type lectin receptors (CLRs) and their downstream signaling kinase SYK. Here we report that the E3 ubiquitin ligase CBLB controls proximal CLR signaling in macrophages and dendritic cells. We show that CBLB associates with SYK and ubiquitinates SYK, dectin-1, and dectin-2 after fungal recognition. Functionally, CBLB deficiency results in increased inflammasome activation, enhanced reactive oxygen species production, and increased fungal killing...
August 2016: Nature Medicine
Yun Xiao, Juan Tang, Hui Guo, Yixia Zhao, Rong Tang, Song Ouyang, Qiuming Zeng, Chad A Rappleye, Murugesan V S Rajaram, Larry S Schlesinger, Lijian Tao, Gordon D Brown, Wallace Y Langdon, Belinda T Li, Jian Zhang
Disseminated candidiasis has become one of the leading causes of hospital-acquired blood stream infections with high mobility and mortality. However, the molecular basis of host defense against disseminated candidiasis remains elusive, and treatment options are limited. Here we report that the E3 ubiquitin ligase CBLB directs polyubiquitination of dectin-1 and dectin-2, two key pattern-recognition receptors for sensing Candida albicans, and their downstream kinase SYK, thus inhibiting dectin-1- and dectin-2-mediated innate immune responses...
August 2016: Nature Medicine
Junmin Zhou, Sarah S Donatelli, Danielle L Gilvary, Melba M Tejera, Erika A Eksioglu, Xianghong Chen, Domenico Coppola, Sheng Wei, Julie Y Djeu
Myeloid-derived suppressor cells (MDSCs) constitute a key checkpoint that impedes tumor immunity against cancer. Chemotherapeutic intervention of MDSCs has gained ground as a strategy for cancer therapy but its mechanism remains obscure.We report here a unique mechanism by which monocytic (M)-MDSCs are spared, allowing them to polarize towards M1 macrophages for reactivation of immunity against breast cancer. We first demonstrated that curcumin, like docetaxel (DTX), can selectively target CD11b(+)Ly6G(+)Ly6C(low) granulocytic (G)-MDSCs, sparing CD11b(+)Ly6G(-)Ly6C(high) M-MDSCs, with reduced tumor burden in 4T1-Neu tumor-bearing mice...
2016: Scientific Reports
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