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Abstract: Regulatory T (Treg) cells induce immune tolerance by suppressing host immune responses against self- or non-self-antigens. Hence, they not only play critical roles in preventing autoimmune diseases, but also may have detrimental effects on vaccines directed to cancer and infectious diseases. Understanding the antigen specificity and functional control of Treg cells will be crucial to the development of effective cancer immunotherapy. This review will discuss different subsets of Treg cells, the factors that contribute to Treg cell generation and suppressive function, and the ability of signaling through Toll-like receptor 8 to reverse the suppressive function of Treg cells. Importantly, this TLR pathway does not depend on interaction with dendritic cells, but operates independently in Treg cells, relying on TLR8 (with MyD88 as its sole receptor-proximal adaptor) to transduce signals generated by TLR8 ligands. Linking TLR signaling to the functional control of Treg cells opens intriguing opportunities to shift the balance between CD4+ T-helper and Treg cells, in ways that may improve the outcome of cancer immunotherapy. [Copyright &y& Elsevier]

Abstract: Regulatory T (Treg) cells induce immune tolerance by suppressing host immune responses against self- or non-self-antigens, thus playing critical roles in preventing autoimmune diseases. However, tumor cells may take advantage of Treg cells to protect themselves from immune attack elicited by vaccines. Recent studies demonstrate the presence of Treg cells in various types of cancers and their suppressive function. Therefore, Treg cells at tumor sites have detrimental effects on immunotherapy directed to cancer and infectious diseases. This review will discuss antigen specificity of Treg cells, the factors that contribute to Treg cell generation and suppressive function, and their regulation through Toll-like receptor signaling. It was generally though that TLR-mediated recognition of specific structures of invading pathogens initiate innate as well as adaptive immune responses through dendritic cells. New evidence suggests that TLR signaling may directly regulate the suppressive function of Treg cells. Linking TLR signaling to the functional control of Treg cells opens intriguing opportunities to shift the balance between CD4+ T-helper and Treg cells, in ways that may improve the outcome of cancer immunotherapy. [Copyright &y& Elsevier]

Abstract: Regulatory T-cells play essential roles in inducing self-tolerance by suppressing immune responses against self such as autoantigens or non-self-antigens such as tumor and pathogenic antigens. Recent studies demonstrate the existence of CD4+ regulatory T-cells at tumor sites, implying that these Treg cells may induce antigen-specific and local immune tolerance. This review will discuss the natural ligands and their potential roles of tumor-specific CD4+ regulatory T-cells in cancer therapy. [Copyright &y& Elsevier]

A microarray method was developed for the detection of 40 bacterial species reported in the literature to be predominant in the human gastrointestinal tract. The 40 species include seven species each of Bacteroides and Clostridium, six species of Ruminococcus, five species of Bifidobacterium, four species of Eubacterium, two species each of Fusobacterium, Lactobacillus and Enterococcus, and single species each of Collinsella, Eggerthella, Escherichia, Faecalibacterium and Finegoldia. Three 40-mer oligos specific for each bacterial species were designed based on comparison of the 16S rDNA sequences available in the GenBank database, and were used to make the DNA-array on epoxy slides. Using two universal primers, the 16S rRNA gene from bacteria present in fecal samples were amplified and labeled with Cyanine5-dCTP by PCR, and then hybridized to the DNA-array. After resolving some difficulties caused by sequence conflicts in GenBank and inaccurate reference strains, all 40 bacterial reference species gave positive results. The microarray method was used to screen fecal samples obtained from 11 healthy human volunteers for the presence of these intestinal bacteria. The results indicated that 25–37 of the 40 species could be detected in each fecal sample and that 33 of the species were found in a majority of the samples. [Copyright &y& Elsevier]

Azo dyes represent a major class of synthetic colorants that are ubiquitous in foods and consumer products. Enterococcus faecalis is a predominant member of the human gastrointestinal microflora. Strain ATCC 19433 grew in the presence of azo dyes and metabolized them to colorless products. A gene encoding a putative FMN-dependent aerobic azoreductase that shares 34% identity with azoreductase (AcpD) of Escherichia coli has been identified in this strain. The gene in E. faecalis, designated as azoA, encoded a protein of 208 amino acids with a calculated isoelectric point of 4.8. AzoA was heterologously overexpressed in E. coli with a strong band of 23 kDa on SDS–PAGE. The purified recombinant enzyme was a homodimer with a molecular weight of 43 kDa, probably containing one molecule of FMN per dimer. AzoA required FMN and NADH, but not NADPH, as a preferred electron donor for its activity. The apparent Km values for both NADH and 2-[4-(dimethylamino)phenylazo]benzoic acid (Methyl red) substrates were 0.14 and 0.024 mM, respectively. The apparent Vmax was 86.2 μM/min/mg protein. The enzyme was not only able to decolorize Methyl red, but was also able to convert sulfonated azo dyes Orange II, Amaranth, Ponceau BS, and Ponceau S. AzoA is the first aerobic azoreductase to be identified and characterized from human intestinal gram-positive bacteria. [Copyright &y& Elsevier]

Guillain–Barre Syndrome (GBS) is a neuromuscular disorder and campylobacteriosis is known to trigger the onset of the disorder. A polymerase chain reaction (PCR) protocol was developed that could specifically amplify a 497-bp region of the UDP-galactose 4-epimerase (galE) gene sequence in campylobacters responsible for triggering the onset of GBS. The identity of the PCR product was confirmed by HindIII endonuclease restriction digestion, which produced the predicted 430 and 67-bp DNA fragments. The assay could detect the presence of the gene in Campylobacter suspensions containing as few as 5 cells ml−1. The assay detected the presence of the gene in 17 of the 20 campylobacters isolated from chicken, 9 of the 13 campylobacters isolated from turkey and 7 of the 7 campylobacters isolated from human stools. All Campylobacter strains isolated from chicken, turkey and clinical samples were resistant to multiple antibiotics. The assay failed to detect the presence of the gene in five different microaerophilic strains of Helicobacter spp., E. coli and Salmonella spp. The entire diagnostic assay, including template preparation, amplification and electrophoresis, can be completed within 6 h. [Copyright &y& Elsevier]

CD4+ T cells play a central role in orchestrating host immune responses against cancer as well as autoimmune and infectious diseases. Identification of major histocompatibility complex (MHC) class II-restricted helper T peptides is important for development of effective vaccines. The lack of effective methods to identify such T-cell peptides is a major hurdle in the use of antigen-specific CD4+ T cells in cancer vaccines. Here we describe a genetic targeting expression system for cloning genes encoding for MHC class II-restricted tumor antigens recognized by tumor-reactive CD4+ T cells. Helper T peptides are subsequently identified by using synthetic peptides to test their ability to stimulate CD4+ T cells. [Copyright &y& Elsevier]

Highlights: [•] TgMAPK1 is a Toxoplasma gondii mitogen-activated protein kinase (MAPK). [•] It affects parasite proliferation in an IFN-γ, iNOS and MKK3-dependent manner. [•] Parasite tissue burden is regulated by TgMAPK1 expression in iNOS-replete tissues. [•] Thus TgMAPK1 ultimately affects virulence by manipulating host IFN-γ-mediated iNOS. [ABSTRACT FROM AUTHOR]