Vi capsular polysaccharide (Vi) was first identified as a virulence antigen of Salmonella typhi , the causative agent typhoid fever in humans; it renders S. resistant to phagocytosis and action serum complement. However, role during infection intestinal epithelium with is not completely understood. We show here that can interact model human epithelial cell line, Caco-2, through cell-surface-associated molecular complex containing two major proteins 30 35 kDa minor protein ≈68 kDa. The were...

Abstract Background Tumor cell-monocyte interactions play crucial roles in shaping up the pro-tumorigenic phenotype and functional output of tumor-associated macrophages. Within tumor microenvironment, such heterotypic cell–cell are known to occur via secretory proteins. Secretory proteins establish a diabolic liaison between cells monocytes, leading their recruitment, subsequent polarization consequent progression. Methods We co-cultured model lung adenocarcinoma cell line A549 with THP-1...

T cells produce a number of cytokines and chemokines upon stimulation with TLR agonists in the presence or absence TCR signals. Here, we show that secretion neutrophil chemoattractant CXCL8 from human cell line Jurkat response to is reduced when carried out serum. Serum does not, however, inhibit TCR-activated nor it down-regulate TLR-costimulated IL-2 activated cells. The molecule can mimic ability bring about suppression TLR-activated serum-borne bioactive lipid, S1P. S1P-mediated...

Several lines of evidence indicate that Fibronectin Extra Domain A (EDA) promotes metastatic capacity tumor cells by engaging cell surface α9β1 integrins. This interaction mediated the C-C loop EDA activates pro-oncogenic signaling pathways leading to epithelial mesenchymal transition (EMT) cells, thus signifying its importance in control progression. In this context present study was designed explore active compounds from selected ethno-medicinal plants western Himalayan region for...

T cells are critical to immunity against pathogenic Salmonella including Typhi which causes systemic infection, typhoid, in humans. The strategies that this pathogen employs keep T-cell mediated immune responses check during establishment of infection not completely understood. Here, we show the virulence polysaccharide Vi, distinguishes S. from localized gastroenteritis-producing nontyphoidal serovars, is a potent inhibitor activation. Vi released by interacts with membrane prohibitin...

TLRs have a fundamental role in immunity. We recently reported that stimulation of TLR2 and TLR5 freshly isolated activated human T cells with microbial ligands without concomitant activation through the TCR brings about secretion neutrophil chemoattractant, CXCL8, effector cytokine, IFN-γ, respectively. However, mechanism TLR signaling has not been worked out. Here, we show Src family kinases, p56 lck (Lck) p59 fyn (Fyn), which are essential for TCR, also critical signal transduction cells....

Lysophosphatidylcholine (LPC), a dominant lipid component of oxidized low-density lipoprotein, plays major role in inflammation associated with atherosclerosis and neurodegenerative disorders. It activates inflammatory responses from macrophages, neuronal cells, endothelial cells. However, the exact mechanism by which LPC promotes remains incompletely understood. In this study, we show that production cytokines cytotoxicity are both critically dependent on its ability to bring about release...

Abstract Tumor‐associated macrophages (TAMs) play a pivotal role in facilitating tumor growth and metastasis. This tumor‐promoting propensity of TAMs sets as result their complex cross‐talk with cells mediated primarily by cell‐secreted proteins the microenvironment. To explore such interactions, we employed an immunoscreening approach involving immunization Balb‐c mice model human lung carcinoma cell line, A549. From serological examination combined mass spectrometric analysis,...

Vi capsular polysaccharide is a major virulence determinant of the human typhoid- causing pathogen Salmonella typhi; it absent in nontyphoidal serovars. We show this study that through its specific interaction with membrane recognition complex containing prohibitin family molecules, can inhibit production inflammatory cytokines from mononuclear phagocytes stimulated flagellin. Remarkably, lost anti-inflammatory capability and switched to proinflammatory state when cell stimulations were...

Abstract TLRs recognize conserved pathogen associated molecular patterns and generate innate immune responses. Several circulating cell membrane proteins have been shown to collaborate with in sensing microbial ligands promoting inflammatory Here, we show that serum serum-borne lipids including lysophosphatidylcholine (LPC) amplify responses from intestinal epithelial cells mononuclear phagocytes primed TLR ligands. Treatment the inhibitors of G protein-coupled receptor (GPCR) signaling,...

Pathogenic Salmonella species initiate infection by invading non-phagocytic intestinal epithelial cells (IEC). This invasion is brought about a number of promoting molecules (Sips) encoded the Pathogenicity Island - 1 (SPI-1). Intracellular delivery some these also brings caspase-1 mediated pyroptotic cell death that contributes to pathogen clearance. These are secreted and delivered inside upon contact with one or more host signals whose identity has not been established. We show...

Pathogenic Salmonella serovars are a major cause of enteric illness in humans and animals, produce clinical manifestations ranging from localized gastroenteritis to systemic disease. T cells critical component immunity against this intracellular pathogen. The mechanisms by which modulates T-cell – mediated immune responses order establish infection not completely understood. We show that mice with enterica serovar Typhimurium (S.Typhimurium) suppresses IL-2 increases IFN- IL-17 production...

Significance While the effect of bacterial molecules on host immune system is well studied, how factors affect expression less appreciated. Here we uncover impact inflammasome activation and type 1 interferon flagellin. Flagellin induces NLRC4 inflammasome-mediated pyroptosis causing clearance Salmonella . We show that also produces lysophospholipids which increase flagellin by early in infection. further demonstrate as infection progresses, IFN inhibits lysophospholipid synthesis, resulting...

Abstract Vi is a linear homopolymer of 1,4 N-acetyl galactosaminuronic acid. It present in S. typhi and some other members Enterobacteriaceae. antigen has been associated with the virulence organism vaccine based upon this found to confer immunity against typhoid. In paper, we report production characterization four hybrid cell clones secreting monoclonal antibodies capsular polysaccharide. Binding analysis using different derivatives showed that three reacted antigenic determinant...

Vi capsular polysaccharide (Vi) is a major virulence factor of human typhoid-causing pathogen Salmonella enterica serovar Typhi (S.Typhi). It distinguishes S.Typhi from closely related non-typhoidal serovars such as S.Typhimurium which do not normally cause systemic infection in humans. only forms capsule around but it also readily released this pathogen. We have previously reported that targets prohibitin to inhibit cellular responses activated through immune receptors. Here, we show...

Fifteen monoclonal antibodies (MAbs) directed against Salmonella typhi were produced and characterized. The specificities of the determined by their binding patterns in an enzyme immunoassay, with a panel lipopolysaccharides isolated from different bacteria. Seven MAbs reacted S. typhi, enteritidis, dublin (all belonging to serogroup D). One MAb also paratyphi A B. Five dublin, Two did not bind any lipopolysaccharide but showed reactivity bacterial sonic extracts A, B, Escherichia coli,...

Toll-like receptors (TLRs) play a major part in providing innate immunity against pathogenic microorganisms. Recent studies show that these are also expressed on T cells, which the sentinels of adaptive immunity. Here, we have investigated regulatory role T-cell receptor functioning cells. We freshly isolated human CD4(+) cells readily secrete neutrophil chemoattractant CXCL8 upon activation with TLR ligands Pam3CSK and flagellin. In contrast, TCR-activated considerably less but start...

Abstract We have used T cells bearing TCRs that are closely related in sequence as probes to detect conformational variants of peptide-MHC complexes murine experimental autoimmune encephalomyelitis H-2u mice. The N-terminal epitope myelin basic protein (MBP) is immunodominant this model. Our studies primarily focused on cell recognition a position 4 analog peptide (MBP1–9[4Y]) complexed with I-Au. Using site-directed mutagenesis, we mapped the functionally important complementarity...

Polymyxin B, used to treat infections caused by antibiotic-resistant Gram-negative bacteria, produces nephrotoxicity at its current dosage. We show that a combination of nonbactericidal concentration this drug and lysophosphatidylcholine (LPC) potently inhibits growth Salmonella least two other bacteria in vitro This makes bacterial membrane porous causes degradation DnaK, the regulator protein folding. B-LPC may be an effective safer regimen against drug-resistant bacteria.

Abstract Enzyme immunoassays were developed using monoclonal antibodies raised against somatic (O), flagellar (H) and capsular (Vi) antigens of Salmonella typhi. The assay based on anti-O could specifically detect S. typhi soluble lipopolysaccharide (LPS) isolated from Anti-H MoAbs detected motile antigen. Monoclonal polysaccharide Vi-containing as well Vi three assays reported here with 100% sensitivity in blood culture broths obtained bacteriologically confirmed typhoid patients negative...

Two hybrid cell clones secreting monoclonal antibodies against flagellar antigen isolated from Salmonella typhi, were produced and characterized. The bound specifically to the strain of S.typhi did not show any reactivity with aflagellar or strains S.dublin, S.paratyphi A, B, S.typhimurium, E.coli, Pseudomonas aeruginosa Klebsiella pneumoniae. recognized a determinant present on group proteins migrating between 45 Kd 60 Kd. These would be useful reagents for clinical epidemiological studies.