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Marisa Benagiano

Publications and source records attributed to Marisa Benagiano.

11 recordsLinked to original sources
PubMed2006

The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses.

The Helicobacter pylori neutrophil-activating protein (HP-NAP) is a virulence factor of H. pylori that stimulates in neutrophils high production of oxygen radicals and adhesion to endothelial cells. We report here that HP-NAP is a TLR2 agonist able to induce the expression of IL-12 and IL-23 by neutrophils and monocytes. Addition in culture of HP-NAP, as an immune modulator, to antigen-induced T cell lines resulted in a remarkable increase in the number of IFN-gamma-producing T cells and decrease of IL-4-secreting cells, thus shifting the cytokine profile of antigen-activated human T cells from Th2 to a Th1 cytotoxic phenotype. We also found that in vivo HP-NAP elicited an antigen-specific Th1-polarized T cell response in the gastric mucosa of H. pylori-infected patients. These data indicate HP-NAP as an important factor of H. pylori able to elicit cells of the innate immune system to produce IL-12 and IL-23, and they suggest it as a new tool for promoting Th1 immune responses.

Adult↗
PubMed2005

Human 60-kDa heat shock protein is a target autoantigen of T cells derived from atherosclerotic plaques.

Epidemiological studies suggest the potential importance of an inflammatory component in atherosclerosis and support the hypothesis that immune responses to Ags of pathogens cross-react with homologous host proteins due to molecular mimicry. Protein candidates involved may be the stress-induced proteins known as heat shock proteins (HSP). In this study, we report that atherosclerotic plaques harbor in vivo-activated CD4(+) T cells that recognize the human 60-kDa HSP. Such in vivo-activated 60-kDa HSP-specific T cells are not detectable in the peripheral blood. In patients with positive serology and PCR for Chlamydia pneumoniae DNA, but not in patients negative for both, most of plaque-derived T cells specific for human 60-kDa HSP also recognized the C. pneumoniae 60-kDa HSP. We characterized the submolecular specificity of such 60-kDa HSP-specific plaque-derived T cells and identified both the self- and cross-reactive epitopes of that autoantigen. On challenge with human 60-kDa HSP, most of the plaque-derived T cells expressed Th type 1 functions, including cytotoxicity and help for monocyte tissue factor production. We suggest that arterial endothelial cells, undergoing classical atherosclerosis risk factors and conditioned by Th type 1 cytokines, express self 60-kDa HSP, which becomes target for both autoreactive T cells and cross-reactive T cells to microbial 60-kDa HSP via a mechanism of molecular mimicry. This hypothesis is in agreement with the notion that immunization with HSP exacerbates atherosclerosis, whereas immunosuppression and T cell depletion prevent the formation of arteriosclerotic lesions in experimental animals.

Aged↗
PubMed2005

Helicobacter pylori, T cells and cytokines: the "dangerous liaisons".

Helicobacter pylori infection is the major cause of gastroduodenal pathologies, but only a minority of infected patients develop chronic and life threatening diseases, as peptic ulcer, gastric cancer, B-cell lymphoma, or autoimmune gastritis. The type of host immune response against H. pylori is crucial for the outcome of the infection. A predominant H. pylori-specific Th1 response, characterized by high IFN-gamma, TNF-alpha, and IL-12 production associates with peptic ulcer, whereas combined secretion of both Th1 and Th2 cytokines are present in uncomplicated gastritis. Gastric T cells from MALT lymphoma exhibit abnormal help for autologous B-cell proliferation and reduced perforin- and Fas-Fas ligand-mediated killing of B cells. In H. pylori-infected patients with autoimmune gastritis cytolytic T cells infiltrating the gastric mucosa cross-recognize different epitopes of H. pylori proteins and H+K+ ATPase autoantigen. These data suggest that peptic ulcer can be regarded as a Th1-driven immunopathological response to some H. pylori antigens, whereas deregulated and exhaustive H. pylori-induced T cell-dependent B-cell activation can support the onset of low-grade B-cell lymphoma. Alternatively, H. pylori infection may lead in some individuals to gastric autoimmunity via molecular mimicry.

Autoimmune Diseases↗
PubMed2004

IFN-gamma-inducible protein 10 and pentraxin 3 plasma levels are tools for monitoring inflammation and disease activity in Mycobacterium tuberculosis infection.

IFN-gamma-inducible protein 10 (IP-10/CXCL10) is a chemokine involved in delayed-type hypersensitivity and attraction of monocytes and activated T lymphocytes at inflammatory foci, whereas pentraxin 3 (PTX3) is part of the innate immune response. In the Republic of Guinea, 220 newly diagnosed, HIV-negative, pulmonary tuberculosis (TB) patients were studied together with 220 healthy household controls and 220 community controls. CXCL10 and PTX3 blood levels were assessed by ELISA at diagnosis, after 2 months and at the end of treatment. In untreated patients, both CXCL10 and PTX3 levels were higher (P < 0.0001) than in controls, although household controls had higher (P < 0.0001) CXCL10 and PTX3 levels than community controls, but lower (P < 0.0001) than those of patients. At the end of treatment, 186 cured patients showed reduction (P < 0.0001) in both CXCL10 and PTX3 levels. In 34 patients with treatment failure, both CXCL10 and PTX3 levels increased further. In five previously healthy households who developed TB during the follow-up and in two patients who relapsed after treatment, a remarkable increase in both CXCL10 and PTX3 plasma levels was observed. Active TB is associated with increased CXCL10 and PTX3 levels in the plasma. Although not specific for TB, measurement of these proteins may help the monitoring of disease activity and efficacy of therapy.

Acute-Phase Proteins↗
PubMed2003

Molecular mimicry between Helicobacter pylori antigens and H+, K+ --adenosine triphosphatase in human gastric autoimmunity.

Autoimmune gastritis and Helicobacter pylori-associated gastric atrophy develop through similar mechanisms involving the proton pump H+,K+-adenosine triphosphatase as autoantigen. Here, we report that H. pylori-infected patients with gastric autoimmunity harbor in vivo-activated gastric CD4+ T cells that recognize both H+, K+-adenosine triphosphatase and H. pylori antigens. We characterized the submolecular specificity of such gastric T cells and identified cross-reactive epitopes from nine H. pylori proteins. Cross-reactive H. pylori peptides induced T cell proliferation and expression of T helper type 1 functions. We suggest that in genetically susceptible individuals, H. pylori infection can activate cross-reactive gastric T cells leading to gastric autoimmunity via molecular mimicry.

Adult↗
PubMed2003

T helper type 1 lymphocytes drive inflammation in human atherosclerotic lesions.

Atherosclerotic lesions are infiltrated by macrophages and T lymphocytes, potentially reactive to pathogens. We studied in vivo activated T lymphocytes that infiltrate atherosclerotic plaques of Helicobacter pylori-infected patients with or without anti-Chlamydia pneumoniae antibodies. In all atherosclerotic lesions, T helper type 1 (Th1) cells were predominant. C. pneumoniae-specific T cells were detected only in the plaques of anti-C. pneumoniae seropositive patients, whereas H. pylori-specific T cells were found in the gastric mucosa but not in the plaques of the same patients. Plaque-derived Th1 cells expressed cytotoxicity, proapoptotic activity, and help for monocyte tissue factor production. Although multifactorial, atherosclerosis can be regarded as a Th1-driven immunopathological condition.

Antibodies, Bacterial↗
PubMed2003

Characterization of H+,K+-ATPase T cell epitopes in human autoimmune gastritis.

Human autoimmune gastritis (AIG) is an organ-specific inflammatory disorder leading to gastric atrophy and pernicious anemia. Gastric H+,K(+)-ATPase was identified as the autoantigen in both human disease and experimental murine AIG (EAIG). Studies of EAIG significantly contributed to current knowledge of human AIG, but to what extent EAIG mimics AIG is still debated, and the autoantigenic epitopes in AIG are yet unknown. This study aimed to identify the H+,K(+)-ATPase epitopes recognized by gastric T cell clones from AIG patients, to define their TCR Vbeta usage and epitope-induced cytokine response. Sixteen H+,K(+)-ATPase-reactive CD4+ gastric T cell clones of four AIG patients were tested for proliferation to overlapping 15-mer peptides spanning the a and beta chains of H+,K(+)-ATPase. We identified 6 epitopes in the a chain and 5 in the beta chain; TCR Vbeta usage was not restricted. Four (36%) of the 11 H+,K(+)-ATPase epitopes recognized in AIG were found to overlap with epitopes that are relevant in EAIG, including a previously described gastritogenic epitope. Gastric T cell recognition of the peptide epitopes resulted in secretion of Th1 cytokines. Our data suggest a striking similarity between human AIG and EAIG, at the epitope level, with regard to cytokine secretion and likely also with regard to pathogenic mechanisms.

Adult↗
PubMed2002

Active tuberculosis in Africa is associated with reduced Th1 and increased Th2 activity in vivo.

Activation of Th1 lymphocytes, IFN-gamma production and macrophage activation are crucial in defense against Mycobacteria. In developing countries, Th2 activation and IL-4 production have been associated in vitro with tuberculosis and with poor clinical outcome after treatment. Serological markers of Th1 [soluble lymphocyte activation gene (LAG)-3] and Th2 (IgE, solubleCD30, and CCL22/macrophage-derived chemokine) activity were measured in 414 HIV-negative tuberculosis patients from The Gambia and Guinée and in 414 healthy household and community controls. Measurements were repeated during treatment to assess the effect of therapy on Th1/Th2 ratio. At diagnosis, sLAG-3 levels were lower in patients than in community controls (p<0.0001), but were higher in household controls exposed to contact with patients than in community controls (p<0.0001). In comparison with community controls, patients had consistently higher levels of IgE, sCD30, and CCL22 (p<0.0001), whereas household controls had lower levels of indicators of Th2 activity (p<0.0001). After treatment, cured patients had higher levels of Th1 (p<0.0001) and lower levels of Th2 (p<0.0001) activity than patients who were not successfully treated or interrupted therapy. In Africa, tuberculosis is associated with low Th1 and high Th2 activity in vivo, whereas close exposure to tuberculosis is associated with a high Th1/Th2 ratio. Patients with favorable outcome after treatment exhibit a higher Th1/Th2 ratio compared to patients with poor clinical outcome.

Adolescent↗
PubMedDate not supplied

Molecular specificity and functional properties of autoreactive T-cell response in human gastric autoimmunity.

Human autoimmune gastritis (AIG) is a chronic inflammatory disorder of the gastric corpus. We have defined the antigen repertoire and the functional properties of in vivo activated CD4+ T cells derived from the gastric mucosa of patients with AIG. A remarkable proportion of the CD4+ T cell clones proliferated in response to H+,K+-ATPase. Six epitopes identified in the alpha chain, and 5 in the beta chain, of gastric K+,K+-ATPase were recognized by autoreactive gastric T cell clones. The majority of the autoreactive T cell clones secreted IFN-gamma and showed a T helper 1 (Th1) profile. All clones produced TNF-alpha,provided help for B cell immunoglobulin production, expressed perforin-mediated cytotoxicity, and most induced Fas-Fas ligand-mediated apoptosis. Data suggest that activation of gastric H+,K+-ATPase-specific Th1 T cells is crucial in the pathogenesis of human gastric autoimmunity and atrophy.

Amino Acid Sequence↗
PubMedDate not supplied

The story so far: Helicobacter pylori and gastric autoimmunity.

The gastric mucosal pathogen Helicobacter pylori induces autoantibodies directed against the gastric proton pump H+,K+-ATPase in 20-30% of infected patients. The presence of these autoantibodies is associated with severity of gastritis, increased atrophy, and apoptosis in the corpus mucosa, and patients with these autoantibodies infected with H. pylori display histopathological and clinical features that are similar to those of autoimmune gastritis (AIG). This review will focus on the T helper cell responses, cytokines, and adhesion molecules involved in corpus mucosal atrophy in chronic H. pylori gastritis and in AIG, and the role of H. pylori in the onset of AIG.

Anemia, Pernicious↗