Protective activity of mixtures of pneumococcal antigens in infection caused by Streptococcus pneumoniae serotype 3

Introduction. Pneumococcal diseases remain relevant for the whole world. On the one hand, this is due to the high prevalence of pneumococcus and the other hand, the growth of antibiotic-resistant strains and the constant change of clinically significant serotypes of the pathogen.The aim of the research was to study of the protective activity of a mixture of pneumococcal antigens.Material and methods. we used preparations of a capsular polysaccharide (CPS) obtained from Streptococcus pneumoniae serotype 3; protein-containing fraction (PCF) obtained from an aqueous extract of cells of S. pneumoniae serotype 6B; recombinant pneumolysin (rPly). Mice were immunized intraperitoneally twice with an interval of 14 days with mixtures of bacterial antigens: CPS + PCF; CPS + rPly; PCF + rPly. To assess the protective activity of the studied drugs after double immunization animals were infected intraperitoneally with S. pneumoniae serotype 3. To study the effect of mixtures of bacterial preparations on the infectious process in the lungs immunized mice were infected with S. pneumoniae serotype 3. The humoral immune response was studied with IgG using the method of ELISA.Results. The CPS + rPly mixture protected mice from intraperitoneal infection with S. pneumoniae serotype 3 regardless of the infecting dose. Immunization with CPS + PCF or CPS + rPly mixtures influenced a significant decrease the number of seeded bacterial cells from lungs during the entire observation period (72 h) compared to the control. Administration of mixtures of bacterial antigens of CPS + PCF, CPS + rPly or PCF + rPly to animals led to a significant increase of the level of antibodies to all antigens, however, the highest levels of IgG were determined to PCF and rPly.Conclusion. The results obtained suggest that different antigenic drugs in mixtures affect different mechanisms of immunity activation.

ML218 HCl Is More Efficient Than Capsaicin in Inhibiting Bacterial Antigen-Induced Cal 27 Oral Cancer Cell Proliferation

The bacterial antigen, lipopolysaccharide (LPS) and disruptions in calcium channels are independently known to influence oral cancer progression. Previously, we found that bacterial antigens, LPS and lipoteichoic acid (LTA) act as confounders during the action of capsaicin on Cal 27 oral cancer proliferation. As calcium channel drugs may affect oral cancer cell proliferation, we investigated the effect of ML218 HCl, a T-type voltage-gated calcium channel blocker, on the proliferation of Cal 27 oral cancer cells. We hypothesized that ML218 HCl could effectively reduce LPS-induced oral cancer cell proliferation. LPS and LTA antigens were added to Cal 27 oral cancer cells either prior to and/or concurrently with ML218 HCl treatment, and the efficacy of the treatment was evaluated by measuring Cal 27 proliferation, cell death and apoptosis. ML218 HCl inhibited oral cancer cell proliferation, increased apoptosis and cell death, but their efficacy was significantly reduced in the presence of bacterial antigens. ML218 HCl proved more effective than capsaicin in reducing bacterial antigen-induced Cal 27 oral cancer cell proliferation. Our results also suggest an interplay of proliferation factors during the bacterial antigens and calcium channel drug interaction in Cal 27. Bacterial antigen reduction of drug efficacy should be considered for developing newer pharmacological agents or testing the efficacy of the existing oral cancer chemotherapeutic agents. Finally, voltage gated calcium channel drugs should be considered for future oral cancer research.

Bacterial Antigens Reduced the Inhibition Effect of Capsaicin on Cal 27 Oral Cancer Cell Proliferation

Oral cancer is a major global health problem with high incidence and low survival rates. The oral cavity contains biofilms as dental plaques that harbour both Gram-negative and Gram-positive bacterial antigens, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), respectively. LPS and LTA are known to stimulate cancer cell growth, and the bioactive phytochemical capsaicin has been reported to reverse this effect. Here, we tested the efficacy of oral cancer chemotherapy treatment with capsaicin in the presence of LPS, LTA or the combination of both antigens. LPS and LTA were administered to Cal 27 oral cancer cells prior to and/or concurrently with capsaicin, and the treatment efficacy was evaluated by measuring cell proliferation and apoptotic cell death. We found that while capsaicin inhibits oral cancer cell proliferation and metabolism (MT Glo assay) and increases cell death (Trypan blue exclusion assay and Caspase 3/7 expression), its anti-cancer effect was significantly reduced on cells that are either primed or exposed to the bacterial antigens. Capsaicin treatment significantly increased oral cancer cells’ suppressor of cytokine signalling 3 gene expression. This increase was reversed in the presence of bacterial antigens during treatment. Our data establish a rationale for clinical consideration of bacterial antigens that may interfere with the treatment efficacy of oral cancer.

The JAK2-STAT pathway epigenetically regulates tolerized genes during the first encounter with bacterial antigens

ABSTRACTMicrobial challenges, such as widespread bacterial infection, induce endotoxin tolerance. This state of hyporesponsiveness to subsequent infections is mainly displayed by monocytes and macrophages. Endotoxin tolerance is generally acquired following a septic episode. In this study, we investigated DNA methylation changes during the acquisition of in vitro tolerance. We identified a set of TET2-mediated demethylation events that are specific to toll-like receptor (TLR) 2 and TLR4 stimulation. Lipopolysaccharide (LPS)-specific demethylation occurs at genomic sites that have low accessibility in quiescent monocytes, concomitantly with the transcriptional activation of many inflammation-related genes, and they are enriched in binding motifs for several signal transducer and activator of transcription (STAT) family members. Indeed, STAT1, STAT3 and STAT5, elements of the JAK2 pathway, are phosphorylated in association with the acquisition of endotoxin tolerance. Inhibition of the JAK2 pathway impairs the activation of tolerized genes on the first encounter with LPS. This is evidence of a crucial role for this pathway in determining the initial response of these genes to bacterial antigens and provides a pharmacological target to prevent exacerbated responses, allowing regulated responses upon subsequent challenges. Finally, we assess the pathological relevance of the JAK2 pathway in monocytes from patients with sepsis.

T Cell Immunity to Bacterial Pathogens: Mechanisms of Immune Control and Bacterial Evasion

The human body frequently encounters harmful bacterial pathogens and employs immune defense mechanisms designed to counteract such pathogenic assault. In the adaptive immune system, major histocompatibility complex (MHC)-restricted αβ T cells, along with unconventional αβ or γδ T cells, respond to bacterial antigens to orchestrate persisting protective immune responses and generate immunological memory. Research in the past ten years accelerated our knowledge of how T cells recognize bacterial antigens and how many bacterial species have evolved mechanisms to evade host antimicrobial immune responses. Such escape mechanisms act to corrupt the crosstalk between innate and adaptive immunity, potentially tipping the balance of host immune responses toward pathological rather than protective. This review examines the latest developments in our knowledge of how T cell immunity responds to bacterial pathogens and evaluates some of the mechanisms that pathogenic bacteria use to evade such T cell immunosurveillance, to promote virulence and survival in the host.

Saliva and Serum Immune Responses in Apical Periodontitis

Apical periodontitis is an inflammatory reaction at the apex of an infected tooth. Its microbiota resembles that of marginal periodontitis and may induce local and systemic antibodies binding to bacteria- and host-derived epitopes. Our aim was to investigate the features of the adaptive immune response in apical periodontitis. The present Parogene cohort (n = 453) comprises patients with cardiac symptoms. Clinical and radiographic oral examination was performed to diagnose apical and marginal periodontitis. A three-category endodontic lesion score was designed. Antibodies binding to the bacteria- and host-derived epitopes were determined from saliva and serum, and bacterial compositions were examined from saliva and subgingival samples. The significant ORs (95% CI) for the highest endodontic scores were observed for saliva IgA and IgG to bacterial antigens (2.90 (1.01–8.33) and 4.91 (2.48–9.71)/log10 unit), saliva cross-reacting IgG (2.10 (1.48–2.97)), serum IgG to bacterial antigens (4.66 (1.22–10.1)), and Gram-negative subgingival species (1.98 (1.16–3.37)). In a subgroup without marginal periodontitis, only saliva IgG against bacterial antigens associated with untreated apical periodontitis (4.77 (1.05–21.7)). Apical periodontitis associates with versatile adaptive immune responses against both bacterial- and host-derived epitopes independently of marginal periodontitis. Saliva immunoglobulins could be useful biomarkers of oral infections including apical periodontitis—a putative risk factor for systemic diseases.

Is ACOS an independent nosology? Clinical signs and diagnosis of ACOS

The aim of this study was to analyze inflammation features and possible causes of asthma-COPD overlap syndrome (ACOS). Methods. Clinical examination was performed for all patients included in the study. Blood levels of alpha-1-antitripsin (AAT), immunoglobulin (Ig) G and E antibodies against four bacterial antigens (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria perflava, and Staphylococcus aureus), and lung function were measured in all the patients. Results. The study involved 175 patients including 78 patients with bronchial asthma, 39 patients with ACOS, 38 patients with COPD, and 20 healthy individuals. AAT blood level was reversely related to lung function and to increased IgG-antibody levels against bacterial antigens. Conclusion. Due to this fact, the authors suppose that the ACOS should be considered as an independent nosology distinct from asthma and COPD, and related to microbial inflammation and AAT level.