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MyD88 in T cells

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https://www.readbyqxmd.com/read/28220116/cpg-odn-shapes-alum-adjuvant-activity-signaling-via-myd88-and-il-10
#1
Luciana Mirotti, Ricardo Wesley Alberca Custódio, Eliane Gomes, Florencia Rammauro, Eliseu Frank de Araujo, Vera Lucia Garcia Calich, Momtchilo Russo
Aluminum-containing adjuvants usually referred as Alum are considered as T helper type-2 (Th2) adjuvants, while agonists of toll-like receptors (TLRs) are viewed as adjuvants that favor Th1/Th17 immunity. Alum has been used in numerous vaccine formulations; however, its undesired pro-Th2 adjuvant activity constitutes a caveat for Alum-based vaccines. Combining Alum with TLR-dependent, pro-Th1/Th17 adjuvants might dampen the pro-Th2 activity and improve the effectiveness of vaccine formulations. Here, using the ovalbumin (OVA) model of allergic lung inflammation, we found that sensitization with the synthetic TLR9 agonist, which is composed of oligodeoxynucleotides containing CpG motifs adsorbed to Alum, inhibited the development of OVA-induced lung allergic Th2 responses without shifting toward a Th1 pattern...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28193909/rv2299c-a-novel-dendritic-cell-activating-antigen-of-mycobacterium-tuberculosis-fused-esat-6-subunit-vaccine-confers-improved-and-durable-protection-against-the-hypervirulent-strain-hn878-in-mice
#2
Han-Gyu Choi, Seunga Choi, Yong Woo Back, Seungwha Paik, Hye-Soo Park, Woo Sik Kim, Hongmin Kim, Seung Bin Cha, Chul Hee Choi, Sung Jae Shin, Hwa-Jung Kim
Understanding functional interactions between DCs and antigens is necessary for achieving an optimal and desired immune response during vaccine development. Here, we identified and characterized protein Rv2299c (heat-shock protein 90 family), which effectively induced DC maturation. The Rv2299c-maturated DCs showed increased expression of surface molecules and production of proinflammatory cytokines. Rv2299c induced these effects by binding to TLR4 and stimulating the downstream MyD88-, MAPK- and NF-κB-dependent signaling pathways...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28176791/il-36%C3%AE-is-a-crucial-proximal-component-of-protective-type-1-mediated-lung-mucosal-immunity-in-gram-positive-and-negative-bacterial-pneumonia
#3
M A Kovach, B Singer, G Martinez-Colon, M W Newstead, X Zeng, P Mancuso, T A Moore, S L Kunkel, M Peters-Golden, B B Moore, T J Standiford
Interleukin-36γ (IL-36γ) is a member of novel IL-1-like proinflammatory cytokine family that are highly expressed in epithelial tissues and several myeloid-derived cell types. Little is known about the role of the IL-36 family in mucosal immunity, including lung anti-bacterial responses. We used murine models of IL-36γ deficiency to assess the contribution of IL-36γ in the lung during experimental pneumonia. Induction of IL-36γ was observed in the lung in response to Streptococcus pneumoniae (Sp) infection, and mature IL-36γ protein was secreted primarily in microparticles...
February 8, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28166680/opposing-roles-of-b-lymphocyte-subsets-in-atherosclerosis
#4
Tin Kyaw, Peter Tipping, Alex Bobik, Ban-Hock Toh
Atherosclerosis is initiated by cholesterol entry into arteries that triggers chronic immune-inflammatory lesions in the vessels. Early lesions are clinically insignificant but advanced complex lesions and vulnerable rupture prone lesions impact on quality of life and can be life threatening. Rupture of vulnerable atherosclerotic lesions initiates thrombotic occlusion of vital arteries precipitating heart attacks and strokes that remain major killers globally despite therapeutic use of statins to lower blood cholesterol levels...
February 2017: Autoimmunity
https://www.readbyqxmd.com/read/28137851/a-mechanism-for-the-induction-of-type-2-immune-responses-by-a-protease-allergen-in-the-genital-tract
#5
Ji Eun Oh, Dong Sun Oh, Hi Eun Jung, Heung Kyu Lee
The genital mucosa is a barrier that is constantly exposed to a variety of pathogens, allergens, and external stimuli. Although both allergen exposure and parasite infections frequently occur in the genital area, the mechanism by which immune responses-particularly type 2 immunity-are induced has rarely been studied in the genital mucosa. Here, we demonstrate the induction of T helper type 2 (Th2) immunity in the genital mucosa in response to a model allergen, the protease papain. Intravaginal papain immunization induced type 2 immunity in a manner that was dependent on protease activity and the estrous phase of the mice...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28131813/microrna-146a-induction-during-influenza-h3n2-virus-infection-targets-and-regulates-traf6-levels-in-human-nasal-epithelial-cells-hnecs
#6
Yuqin Deng, Yan Yan, Kai Sen Tan, Jing Liu, Vincent T Chow, Ze-Zhang Tao, De-Yun Wang
We have previously shown that human nasal epithelial cells (hNECs) are highly permissive cells for respiratory viruses including influenza A virus (IAV) and respiratory syncytial virus. Recent studies have indicated that microRNAs (miRNAs) are involved in virus-host relationship, and this led us to investigate its essential roles in the in vitro hNECs model derived from multiple donors. By comparing the differential expression of miRNAs upon IAV infection among animal and cell line studies, candidates were selected with focus on the initial immune response...
January 25, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28126263/treponema-pallidum-flagellins-elicit-proinflammatory-cytokines-from-human-monocytes-via-tlr5-signaling-pathway
#7
Man Xu, Yafeng Xie, Chuanhao Jiang, Yongjian Xiao, Xingxing Kuang, Yating Wen, Yuan Tan, Manyi Tan, Feijun Zhao, Tiebing Zeng, Yimou Wu
The tissue damage caused by syphilis infection may be associated with inflammation. However, the virulence factors of Treponema pallidum are still unclear, nor are the molecular mechanisms for leading to the productions of proinflammatory cytokines. Flagellin, a classic pathogen-associated molecular pattern (PAMP), is a potent immunogen that induces inflammation. In the present study, we have demonstrated that stimulations of human monocytes with Treponema pallidum FlaB1, FlaB2, and FlaB3 result in the up regulation of interleukin (IL)-6 and IL-8...
January 21, 2017: Immunobiology
https://www.readbyqxmd.com/read/28125560/o-012-il-36-signaling-controls-the-induced-regulatory-t-cell-th9-cell-balance-and-gut-inflammation
#8
Akihito Harusato, Hirohito Abo, Vu Ngo, Samuel Yi, Satoru Osuka, Jakob Kohlmeier, Jian-Dong Li, Andrew Gewirtz, Asma Nusrat, Timothy Denning
BACKGROUND: In the United States over 1.4 million people suffer from inflammatory bowel disease (IBD). Therefore, there is a pressing need for the development of novel molecular therapeutics targeting pro-inflammatory mediators. Recently a novel interleukin-1 family member, IL-36γ was shown to be up-regulated in patients with inflammatory bowel disease (IBD) and to play an important role in healing of acute intestinal damage in mice, however, the function of IL-36γ with regards to T helper (TH) cell differentiation during gut inflammation remains undefined...
February 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28111358/identification-of-a-gene-encoding-a-membrane-anchored-toll-like-receptor-5-tlr5m-in-oplegnathus-fasciatus-that-responds-to-flagellin-challenge-and-activates-nf-%C3%AE%C2%BAb
#9
Navaneethaiyer Umasuthan, S D N K Bathige, William Shanthakumar Thulasitha, R G P T Jayasooriya, Younhee Shin, Jehee Lee
Toll-like receptor 5 (TLR5) recognizes bacterial flagellin and induces the downstream signaling through the myeloid differentiation primary response gene 88 (MyD88) protein to produce proinflammatory cytokines. In this study, we describe a TLR5 membrane form (OfTLR5M) and its adaptor protein MyD88 (OfMyD88) in rock bream, Oplegnathus fasciatus. Both Oftlr5m (6.7 kb) and Ofmyd88 (3.7 kb) genes displayed a quinquepartite structure with five exons and four introns. Protein structure of OfTLR5M revealed the conventional architecture of TLRs featured by an extracellular domain with 22 leucine rich repeats (LRR), a transmembrane domain and an endodomain with TIR motif...
January 19, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28110075/tlr9-mediated-regulatory-b10-cell-amplification-following-sub-total-body-irradiation-implications-in-attenuating-eae
#10
Jinsheng Hong, Jie Fang, Ruilong Lan, Qi Tan, Yeping Tian, Mei Zhang, Paul Okunieff, Lurong Zhang, Jianhua Lin, Deping Han
Autoimmunity and inflammation are controlled in part by regulatory B (Breg) cells, including the recently identified IL-10-competent B10 cell subset that represents 1%-3% of mouse spleen B cells. In this study, the influence of irradiation on Breg/B10 cell generation and IL-10 production mediated by TLR9 signaling pathways was investigated. Spleen and peritoneal cavity Breg/B10 cell frequencies were significantly expanded three weeks after sub-total body irradiation (sub-TBI, 5Gy or 10Gy) in adult male wild type (WT) C57BL/6(B6) mice but not in TLR9(-/-) mice...
March 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28110064/activation-of-dendritic-cells-by-low-molecular-weight-oyster-polysaccharides
#11
Ming Zhong, Cheng Zhong, Tingting Wang, Pei Hu, Guanghui Wang, Rujing Ren, Jing Zhang, Huijei Gao, Wen Cui, Wenjuan Duan, Jiantu Che
Dendritic cells play a primary role in antigen presentation to CD4(+) T cells, which initiate acquired immune responses. Therefore, determining positive modulators of dendritic cell activation to improve therapeutic approaches for cancer treatment might be useful. We here investigated the effects of low molecular weight oyster polysaccharides (LMW-OPS) on bone marrow-derived dendritic cells (BMDCs) obtained from mice. LMW-OPS increased the surface expression of major histocompatibility complex class II (MHC-II), CD40 and CD86 in BMDCs and induced the secretion of tumour necrosis factor (TNF)-α and interleukin (IL)-12, which were significantly decreased in the BMDCs derived from MyD88(-/-) mice but not from the lipopolysaccharide-resistant C3H/HeJ mice...
January 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28099848/biophysical-attributes-of-cpg-presentation-control-tlr9-signaling-to-differentially-polarize-systemic-immune-responses
#12
Jardin A Leleux, Pallab Pradhan, Krishnendu Roy
It is currently unknown whether and how mammalian pathogen recognition receptors (PRRs) respond to biophysical patterns of pathogen-associated molecular danger signals. Using synthetic pathogen-like particles (PLPs) that mimic physical properties of bacteria or large viruses, we have discovered that the quality and quantity of Toll-like receptor 9 (TLR9) signaling by CpG in mouse dendritic cells (mDCs) are uniquely dependent on biophysical attributes; specifically, the surface density of CpG and size of the presenting PLP...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28088065/methionine-enkephalin-menk-mounts-antitumor-effect-via-regulating-dendritic-cells-dcs
#13
Yiming Meng, Xinghua Gao, Wenna Chen, Nicolas P Plotnikoff, Noreen Griffin, Guirong Zhang, Fengping Shan
MENK, an endogenous opioid peptide has been reported to have many immunological and antitumor activities. So far the detailed mechanisms of antitumor through regulating DCs by MENK have not been elucidated yet. The aim of this work was to investigate the antitumor mechanisms of MENK via regulating DC. The monitoring methods, such as ELISA, MTS assay, CFSE, Real-time PCR and Western blot were included in our research. We found bone marrow derived dendritic cells (BMDCs) in 36 female C57BL/6 mice treated with MENK enhanced expression of key surface molecules, increased production of critical cytokines reduced endocytosis of FITC-dextran, upregulated TLR4 through MyD88/NF-κB signaling pathway and mounted higher antitumor activity...
January 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28076786/porphyromonas-gingivalis-promotes-unrestrained-type-i-interferon-production-by-dysregulating-tam-signaling-via-myd88-degradation
#14
Gabriel Mizraji, Maria Nassar, Hadas Segev, Hafiz Sharawi, Luba Eli-Berchoer, Tal Capucha, Tsipora Nir, Yaara Tabib, Avraham Maimon, Shira Dishon, Lior Shapira, Gabriel Nussbaum, Asaf Wilensky, Avi-Hai Hovav
Whereas type I interferons (IFNs-I) were proposed to be elevated in human periodontitis, their role in the disease remains elusive. Using a bacterial-induced model of murine periodontitis, we revealed a prolonged elevation in IFN-I expression. This was due to the downregulation of TAM signaling, a major negative regulator of IFN-I. Further examination revealed that the expression of certain TAM components was reduced as a result of prolonged degradation of MYD88 by the infection. As a result of such prolonged IFN-I production, innate immunological functions of the gingiva were disrupted, and CD4(+) T cells were constitutively primed by dendritic cells, leading to elevated RANKL expression and, subsequently, alveolar bone loss (ABL)...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28069819/temporal-role-for-myd88-in-a-model-of-brucella-induced-arthritis-and-musculoskeletal-inflammation
#15
Carolyn A Lacey, William J Mitchell, Charles R Brown, Jerod A Skyberg
Brucella spp. are facultative intracellular Gram-negative bacteria that cause the zoonotic disease brucellosis, one of the most common global zoonoses. Osteomyelitis, arthritis and musculoskeletal inflammation are common focal complications of brucellosis in humans; however, wild-type (WT) mice infected systemically with conventional doses of Brucella do not develop these complications. Here we report WT C57BL/6 mice infected via the footpad with 10(3)-10(6) CFUs of Brucella spp. display neutrophil and monocyte infiltration to the joint space and surrounding musculoskeletal tissue...
January 9, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28056114/diagnosis-and-management-of-waldenstr%C3%A3-m-macroglobulinemia-mayo-stratification-of-macroglobulinemia-and-risk-adapted-therapy-msmart-guidelines-2016
#16
Prashant Kapoor, Stephen M Ansell, Rafael Fonseca, Asher Chanan-Khan, Robert A Kyle, Shaji K Kumar, Joseph R Mikhael, Thomas E Witzig, Michelle Mauermann, Angela Dispenzieri, Sikander Ailawadhi, A Keith Stewart, Martha Q Lacy, Carrie A Thompson, Francis K Buadi, David Dingli, William G Morice, Ronald S Go, Dragan Jevremovic, Taimur Sher, Rebecca L King, Esteban Braggio, Ann Novak, Vivek Roy, Rhett P Ketterling, Patricia T Greipp, Martha Grogan, Ivana N Micallef, P Leif Bergsagel, Joseph P Colgan, Nelson Leung, Wilson I Gonsalves, Yi Lin, David J Inwards, Suzanne R Hayman, Grzegorz S Nowakowski, Patrick B Johnston, Steven J Russell, Svetomir N Markovic, Steven R Zeldenrust, Yi L Hwa, John A Lust, Luis F Porrata, Thomas M Habermann, S Vincent Rajkumar, Morie A Gertz, Craig B Reeder
Importance: Waldenström macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, has witnessed several practice-altering advances in recent years. With availability of a wider array of therapies, the management strategies have become increasingly complex. Our multidisciplinary team appraised studies published or presented up to December 2015 to provide consensus recommendations for a risk-adapted approach to WM, using a grading system. Observations: Waldenström macroglobulinemia remains a rare, incurable cancer, with a heterogeneous disease course...
January 5, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28011934/exogenous-il-33-restores-dendritic-cell-activation-and-maturation-in-established-cancer
#17
Donye Dominguez, Cong Ye, Zhe Geng, Siqi Chen, Jie Fan, Lei Qin, Alan Long, Long Wang, Zhuoli Zhang, Yi Zhang, Deyu Fang, Timothy M Kuzel, Bin Zhang
The role of IL-33, particularly in tumor growth and tumor immunity, remains ill-defined. We show that exogenous IL-33 can induce robust antitumor effect through a CD8(+) T cell-dependent mechanism. Systemic administration of rIL-33 alone was sufficient to inhibit growth of established tumors in transplant and de novo melanoma tumorigenesis models. Notably, in addition to a direct action on CD8(+) T cell expansion and IFN-γ production, rIL-33 therapy activated myeloid dendritic cells (mDCs) in tumor-bearing mice, restored antitumor T cell activity, and increased Ag cross-presentation within the tumor microenvironment...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28003376/selective-irak4-inhibition-attenuates-disease-in-murine-lupus-models-and-demonstrates-steroid-sparing-activity
#18
Shailesh Dudhgaonkar, Sourabh Ranade, Jignesh Nagar, Siva Subramani, Durga Shiv Prasad, Preethi Karunanithi, Ratika Srivastava, Kamala Venkatesh, Sabariya Selvam, Prasad Krishnamurthy, T Thanga Mariappan, Ajay Saxena, Li Fan, Dawn K Stetsko, Deborah A Holloway, Xin Li, Jun Zhu, Wen-Pin Yang, Stefan Ruepp, Satheesh Nair, Joseph Santella, John Duncia, John Hynes, Kim W McIntyre, Julie A Carman
The serine/threonine kinase IL-1R-associated kinase (IRAK)4 is a critical regulator of innate immunity. We have identified BMS-986126, a potent, highly selective inhibitor of IRAK4 kinase activity that demonstrates equipotent activity against multiple MyD88-dependent responses both in vitro and in vivo. BMS-986126 failed to inhibit assays downstream of MyD88-independent receptors, including the TNF receptor and TLR3. Very little activity was seen downstream of TLR4, which can also activate an MyD88-independent pathway...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27997610/effective-respiratory-cd8-t-cell-immunity-to-influenza-virus-induced-by-intranasal-carbomer-lecithin-adjuvanted-non-replicating-vaccines
#19
David J Gasper, Brandon Neldner, Erin H Plisch, Hani Rustom, Emily Carrow, Hirotaka Imai, Yoshihiro Kawaoka, M Suresh
CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonstrated to elicit robust humoral immunity to non-replicating antigens. We report that mice immunized with non-replicating Adjuplex-adjuvanted vaccines generated robust antigen-specific CTL responses...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27996000/central-role-of-cd169-lymph-node-resident-macrophages-in-the-adjuvanticity-of-the-qs-21-component-of-as01
#20
Sophie Detienne, Iain Welsby, Catherine Collignon, Sandrine Wouters, Margherita Coccia, Sophie Delhaye, Laurye Van Maele, Séverine Thomas, Maëlle Swertvaegher, Aurélie Detavernier, Abdelatif Elouahabi, Stanislas Goriely, Arnaud M Didierlaurent
Saponins represent a promising class of vaccine adjuvant. Together with the TLR4-ligand MPL, QS-21 is part of the Adjuvant System AS01, a key component of the malaria and zoster candidate vaccines that display demonstrated clinical efficacy. However, the mechanism of action of QS-21 in this liposomal formulation is poorly understood. Upon intra-muscular immunisation, we observed that QS-21 rapidly accumulated in CD169(+) resident macrophages of the draining lymph node where it elicited a local innate immune response...
December 20, 2016: Scientific Reports
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