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F L Nowrouzian, G Lina, E Hodille, E Lindberg, B Hesselmar, R Saalman, I Adlerberth, A E Wold
According to the hygiene hypothesis, insufficient immune activation by microbes increases the risk of allergy development. Staphylococcus aureus, which is part of the skin and gut microbiota of infants in Western countries, produces a variety of T-cell-activating enterotoxins, called superantigens. We investigated whether early (0-2 months of age) gut colonisation by S. aureus strains that carry specific superantigens and adhesins was related to subsequent development of atopic eczema in a Swedish birth-cohort...
October 19, 2016: British Journal of Dermatology
Akimune Kaga, Hiroshi Watanabe, Hiroki Miyabayashi, Takaya Metoki, Setsuko Kitaoka, Satoru Kumaki
Neonatal toxic shock syndrome-like exanthematous disease (NTED) is a newly recognized neonatal infectious disease, caused by the superantigen toxic shock syndrome toxin-1 (TSST-1). TSST-1 is mainly produced by methicillin-resistant Staphylococcus aureus, and the immune responses to TSST-1 are known to cause toxic shock syndrome, a life-threatening infectious disease. The clinical symptoms of NTED are skin rash, fever, and thrombocytopenia, but severe thrombocytopenia is rare in term infants with NTED. Although the cause of NTED is the same as that of toxic shock syndrome, the clinical symptoms of NTED are milder than toxic shock syndrome...
2016: Tohoku Journal of Experimental Medicine
Yoshie Kametani, Shino Ohshima, Asuka Miyamoto, Atsuko Shigenari, Masaki Takasu, Noriaki Imaeda, Tatsuya Matsubara, Masafumi Tanaka, Takashi Shiina, Hiroshi Kamiguchi, Ryuji Suzuki, Hitoshi Kitagawa, Jerzy K Kulski, Noriaki Hirayama, Hidetoshi Inoko, Asako Ando
The class I major histocompatibility complex (MHC) presents self-developed peptides to specific T cells to induce cytotoxity against infection. The MHC proteins are encoded by multiple loci that express numerous alleles to preserve the variability of the antigen-presenting ability in each species. The mechanism regulating MHC mRNA and protein expression at each locus is difficult to analyze because of the structural and sequence similarities between alleles. In this study, we examined the correlation between the mRNA and surface protein expression of swine leukocyte antigen (SLA)-1*0401 after the stimulation of peripheral blood mononuclear cells (PBMCs) by Staphylococcus aureus superantigen toxic shock syndrome toxin-1 (TSST-1)...
2016: PloS One
Peter L Stern, Richard Harrop
The natural history of a patient's cancer is often characterised by genetic diversity and sequential sweeps of clonal dominance. It is therefore not surprising that identifying the most appropriate tumour-associated antigen for targeted intervention is challenging. The 5T4 oncofoetal antigen was identified by searching for surface molecules shared between human trophoblast and cancer cells with the rationale that they may function to allow survival of the foetus as a semi-allograft in the mother or a tumour in its host...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
Lyudmila Boyanova, Rumyana Markovska, Ivan Mitov
This review focuses on the virulence arsenal of the most pathogenic species among Gram positive anaerobic cocci, Finegoldia magna according to recently published data from 2012-2016. Virulence factors like sortase dependent pili and F. magna adhesion factor (FAF) facilitate the start of the infection. Albumin binding protein (PAB) enhances F. magna survival. FAF, subtilisin-like extracellular serine protease (SufA) and superantigen protein L protect the bacteria from factors of innate defense system. SufA, capsule and tissue-destroying enzymes provide a deep penetration or spread of the infections and the protein L is associated with infection severity...
October 15, 2016: Anaerobe
Guojun Zhang, Mingkai Xu, Huiwen Zhang, Yubo Song, Jian Wang, Chenggang Zhang
Staphylococcal enterotoxin C2 (SEC2), a member of bacterial superantigen, is one of the most potent known activators of T lymphocytes. With this property, SEC2 has already been used in clinic as a tumor immunotherapy agent in China. To increase the antitumor activity, a SEC2 mutant named ST-4 (GKVTG102-106WWH) with amino acid substitutions in T cell receptor (TCR)-binding domain was generated by site-directed mutagenesis, and the molecular mechanism of the enhanced antitumor activity was investigated. Results showed that ST-4 could activate much more Vβ 8...
October 11, 2016: Toxicology and Applied Pharmacology
Jorge L Aguilar, Avanish K Varshney, Ximo Pechuan, Kaushik Dutta, Joshua D Nosanchuk, Bettina C Fries
Staphylococcus aureus is a leading infectious cause of life-threatening disease in humans, yet there is currently no vaccine to combat this bacterium. The pathogenesis of S. aureus is mediated by a diverse array of protein toxins including a large family of secreted pyrogenic superantigens. Neutralization of superantigens, including SEB and TSST-1, has proven to be protective in several animal models of toxic shock and sepsis. We demonstrate, for the first time, that a far more prevalent staphylococcal superantigen, SEK, can also induce lethal shock in mice...
October 7, 2016: Virulence
Revital Levy, Ziv Rotfogel, Dalia Hillman, Andrey Popugailo, Gila Arad, Emmanuelle Supper, Farhat Osman, Raymond Kaempfer
Full T-cell activation requires interaction between the costimulatory receptors B7-2 and CD28. By binding CD28, bacterial superantigens elicit harmful inflammatory cytokine overexpression through an unknown mechanism. We show that, by engaging not only CD28 but also its coligand B7-2 directly, superantigens potently enhance the avidity between B7-2 and CD28, inducing thereby T-cell hyperactivation. Using the same 12-aa β-strand-hinge-α-helix domain, superantigens engage both B7-2 and CD28 at their homodimer interfaces, areas remote from where these coreceptors interact, implying that inflammatory signaling can be controlled through the receptor homodimer interfaces...
October 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
Wilbur H Chen, Marcela F Pasetti, Rajan P Adhikari, Holly Baughman, Robin Douglas, Jill El-Khorazaty, Nancy Greenberg, Frederick W Holtsberg, Grant C Liao, Mardi K Reymann, Xiaolin Wang, Kelly L Warfield, M Javad Aman
: Staphylococcus aureus produces several enterotoxins and superantigens, exposure to which can elicit profound toxic shock. A recombinant staphylococcal enterotoxin B (rSEB), containing 3 distinct mutations in the MHCII binding site, was combined with Alhydrogel as a potential parenteral vaccine named STEBVax.Consenting healthy adult volunteers, age 23-38 years, participated in a first-in-human open label dose-escalation study of parenteral doses of STEBVax ranging from 0.01 μg up to 20 μg...
October 5, 2016: Clinical and Vaccine Immunology: CVI
Qian Liu, Won-Sik Yeo, Taeok Bae
In the Gram-positive pathogenic bacterium Staphylococcus aureus, the SaeRS twocomponent system (TCS) plays a major role in controlling the production of over 20 virulence factors including hemolysins, leukocidins, superantigens, surface proteins, and proteases. The SaeRS TCS is composed of the sensor histidine kinase SaeS, response regulator SaeR, and two auxiliary proteins SaeP and SaeQ. Since its discovery in 1994, the sae locus has been studied extensively, and its contributions to staphylococcal virulence and pathogenesis have been well documented and understood; however, the molecular mechanism by which the SaeRS TCS receives and processes cognate signals is not...
October 3, 2016: Genes
Emre Balta, Julian Stopp, Laura Castelletti, Henning Kirchgessner, Yvonne Samstag, Guido H Wabnitz
Neutrophils or polymorphonuclear cells (PMN) eliminate bacteria via phagocytosis and/or NETosis. Apart from these conventional roles, PMN also have immune-regulatory functions. They can transdifferentiate and upregulate MHCII as well as ligands for costimulatory receptors which enables them to behave as antigen presenting cells (APC). The initial step for activating T-cells is the formation of an immune synapse between T-cells and antigen-presenting cells). However, the immune synapse that develops at the PMN/T-cell contact zone is as yet hardly investigated due to the non-availability of methods for analysis of large number of PMN interactions...
September 27, 2016: Methods: a Companion to Methods in Enzymology
Jiun-Bo Chen, Louisa K James, Anna M Davies, Y-C Wu, Joanne Rimmer, Valerie J Lund, Jou-Han Chen, James M McDonnell, Yih-Chih Chan, George H Hutchins, Tse Wen Chang, Brian J Sutton, Harsha H Kariyawasam, Hannah J Gould
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease (AERD) is a severe form of CRSwNP in which nearly all patients express anti-SAEs. OBJECTIVES: We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions (FRs)...
September 19, 2016: Journal of Allergy and Clinical Immunology
Karol Fijałkowski, Dorota Peitler, Jolanta Karakulska
The aim of this study was to analyse the staphylococci isolated from ready-to-eat meat products, including pork ham, chicken cold cuts, pork sausage, salami and pork luncheon meat, sliced in the store to the consumer's specifications, along with species identification and determination of antibiotic resistance. Genes encoding staphylococcal enterotoxins, staphylococcal enterotoxin-like proteins, exfoliative toxins, and toxic shock syndrome toxin 1 were also investigated. From the 41 samples, 75 different staphylococcal isolates were obtained...
December 5, 2016: International Journal of Food Microbiology
Ben Boursi, Kevin Haynes, Ronac Mamtani, Yu-Xiao Yang
Colonization with staphylococcus aureus (SA) is associated with disease activity and progression in patients with cutaneous T-cell lymphoma (CTCL) secondary to T-cell activation by bacterial superantigens. The aim of the current study was to evaluate the possible role of SA as an etiologic factor affecting CTCL initiation. We conducted a nested case-control study in a large population-representative database from the UK. Cases were defined as all patients with an incident diagnosis of mycosis fungoides (MF) or Sezary syndrome (SS) between 1995 and 2013...
November 2016: Archives of Dermatological Research
Mark J Selby, John J Engelhardt, Robert J Johnston, Li-Sheng Lu, Minhua Han, Kent Thudium, Dapeng Yao, Michael Quigley, Jose Valle, Changyu Wang, Bing Chen, Pina M Cardarelli, Diann Blanset, Alan J Korman
The monoclonal antibodies ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) have shown remarkable antitumor activity in an increasing number of cancers. When combined, ipilimumab and nivolumab have demonstrated superior activity in patients with metastatic melanoma (CHECKMATE-067). Here we describe the preclinical development strategy that predicted these clinical results. Synergistic antitumor activity in mouse MC38 and CT26 colorectal tumor models was observed with concurrent, but not sequential CTLA-4 and PD-1 blockade...
2016: PloS One
Daniela Lorenzo, Alejandra Duarte, Juliana Mundiñano, Paula Berguer, Irene Nepomnaschy, Isabel Piazzon
B-cell superantigens (Sags) bind to conserved sites of the VH or VL regions of immunoglobulin molecules outside their complementarity-determining regions causing the apoptosis of normal cognate B cells. No attempts to investigate whether B-cell Sags are able to induce the apoptosis of cognate malignant B cells were reported. In the present study we show that protein L (PpL), secreted by Finegoldia magna, a B-cell Sag which interacts with κ+ bearing cells, induces the apoptosis of murine and human κ+ lymphoma B cells both in vitro and in vivo...
2016: PloS One
Marjan Islam, Dennis Karter, Jerry Altshuler, Diana Altshuler, David Schwartz, Gianluca Torregrossa
Infections from Streptococcus dysgalactiae ssp. equisimilis (SDSE) can cause a wide variety of infections, ranging from mild cellulitis to invasive disease, such as endocarditis and streptococcal toxic shock-like syndrome (TSLS). Despite prompt and appropriate antibiotics, mortality rates associated with shock have remained exceedingly high, prompting the need for adjunctive therapy. IVIG has been proposed as a possible adjunct, given its ability to neutralize a wide variety of superantigens and modulate a dysregulated inflammatory response...
2016: Case Reports in Infectious Diseases
Dominique Missiakas, Olaf Schneewind
Staphylococcus aureus, a commensal of the human nasopharynx and skin, also causes invasive disease, most frequently skin and soft tissue infections. Invasive disease caused by drug-resistant strains, designated MRSA (methicillin-resistant S. aureus), is associated with failure of antibiotic therapy and elevated mortality. Here we review polysaccharide-conjugate and subunit vaccines that were designed to prevent S. aureus infection in patients at risk of bacteremia or surgical wound infection but failed to reach their clinical endpoints...
August 22, 2016: Journal of Experimental Medicine
Dürdal Us
Superantigens (SAgs) are microbial proteins produced by various microorganisms that elicit excessive and strong stimulation of T cells via an unconventional mechanism. They cause polyclonal activation of T cells in a non-specific manner, by binding to a particular variable-beta (Vβ) chain of T-cell receptor (TCR) and MHC class II molecule, in unprocessed form and outside of peptide-binding cleft, forming a bridge between the antigen presenting cell and the T cell. SAgs are classified into three groups, namely 1) exogenous (soluble proteins and exotoxins secreted by microorganisms), 2) endogenous (transmembrane proteins encoded by viruses which are integrated into the genome) and 3) B-cell SAgs (proteins which stimulate predominantly B cells)...
July 2016: Mikrobiyoloji Bülteni
Katherine J Nicholas, David K Flaherty, Rita M Smith, D Noah Sather, Spyros A Kalams
Peripheral CD4+CXCR5+PD-1+ T cells are a putative circulating counterpart to germinal center T follicular helper (TFH) cells. They show both phenotypic and functional similarities to TFH cells, which provide necessary help for the differentiation of B cells to antibody-secreting plasmablasts. In this study we evaluated the frequency, phenotypes, and responses of peripheral TFH-like (pTFH) cells to superantigen and recall antigen stimulation in 10 healthy and 34 chronically infected treatment-naïve HIV-1+ individuals...
August 5, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
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