Comparison of mucosal B- and T-cell responses in<i>Helicobacter pylori</i>-infected subjects in a developing and a developed country

Bhuiyan, Taufiqur Rahman; Qadri, Firdausi; Bardhan, Prodip Kumar; Ahmad, Mubashir; Kindlund, Bert; Svennerholm, Ann‐Mari; Lundgren, Anna

doi:10.1111/j.1574-695x.2008.00449.x

Cited by 10 publications

(14 citation statements)

References 31 publications

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“…In fact, iNOS + MUM1 + PCs constituted approximately one third of all mucosal iNOS + cells. In contrast, LPLs of control patients contained no or almost no CD19 + B cells or PCs, which is in agreement with previous studies (22,33). Expression of this enzyme is not a general feature of human PCs at gastrointestinal sites because mucosal iNOS + PCs were not detectable in duodenal biopsy specimens of T. whipplei-, HIV-, or G. duodenalis-infected patients, and we also detected iNOS-negative mucosal PCs in H. pylori-infected patients.…”

Section: Discussionsupporting

confidence: 82%

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Mucosal Inducible NO Synthase–Producing IgA+ Plasma Cells in Helicobacter pylori–Infected Patients

Neumann

Mueller

Moos

et al. 2016

The Journal of Immunology

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The mucosal immune system is relevant for homeostasis, immunity, and also pathological conditions in the gastrointestinal tract. Inducible NO synthase (iNOS)–dependent production of NO is one of the factors linked to both antimicrobial immunity and pathological conditions. Upregulation of iNOS has been observed in human Helicobacter pylori infection, but the cellular sources of iNOS are ill defined. Key differences in regulation of iNOS expression impair the translation from mouse models to human medicine. To characterize mucosal iNOS-producing leukocytes, biopsy specimens from H. pylori–infected patients, controls, and participants of a vaccination trial were analyzed by immunohistochemistry, along with flow cytometric analyses of lymphocytes for iNOS expression and activity. We newly identified mucosal IgA-producing plasma cells (PCs) as one major iNOS+ cell population in H. pylori–infected patients and confirmed intracellular NO production. Because we did not detect iNOS+ PCs in three distinct infectious diseases, this is not a general feature of mucosal PCs under conditions of infection. Furthermore, numbers of mucosal iNOS+ PCs were elevated in individuals who had cleared experimental H. pylori infection compared with those who had not. Thus, IgA+ PCs expressing iNOS are described for the first time, to our knowledge, in humans. iNOS+ PCs are induced in the course of human H. pylori infection, and their abundance seems to correlate with the clinical course of the infection.

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Section: Discussionsupporting

confidence: 82%

“…3A). LPLs of control patients contained almost no CD19 + B cells, which is in agreement with previous studies (22). We additionally characterized by flow cytometry the PCs (CD19 + CD20 2 CD27 ++ ) for the expression of CD38, to distinguish them further from mBCs (CD38 2 ), and for iNOS.…”

Section: Early Increase Of Mucosal Inos-expressing Pcs Following H Psupporting

confidence: 73%

Mucosal Inducible NO Synthase–Producing IgA+ Plasma Cells in Helicobacter pylori–Infected Patients

Neumann

Mueller

Moos

et al. 2016

The Journal of Immunology

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“…This finding suggests that gut-homing CD19 ϩ cells may take some time to home back to the gut from the circulatory system. The baseline levels of CD19 ϩ and guthoming CD19 ϩ cells in biopsy specimens were also relatively high in our healthy Bangladeshi controls, perhaps triggered by infection with other pathogens and the resulting recruitment of lymphocytes to this site (3). Further studies are needed to better understand the kinetics of antigen-specific B cell responses in the duodenal mucosa of V. cholerae-infected patients.…”

Section: Discussionmentioning

confidence: 99%

“…LPLs and PBMCs (5 ϫ 10 4 cells per sample with a control) were stained for naïve and memory B cell markers, as well as a gut-homing marker, as described previously (3,23), using anti-CD19-fluorescein isothiocyanate (FITC), anti-␣4 ϩ cell populations were gated from the CD19 ϩ cell population. Control samples showed that contamination between groups was negligible.…”

Section: Methodsmentioning

confidence: 99%

Mucosal Immunologic Responses in Cholera Patients in Bangladesh

Uddin

Harris

Bhuiyan

et al. 2011

Clin Vaccine Immunol

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Vibrio cholerae O1 causes dehydrating diarrhea with a high mortality rate if untreated. The infection also elicits long-term protective immunity. Since V. cholerae is noninvasive, mucosal immunity is likely important for protection. In this study, we compared humoral immune responses in the duodenal mucosa and blood of cholera patients at different time points after the onset of disease and compared them with those of healthy controls (HCs). Immune responses to lipopolysaccharide (LPS) and the recombinant cholera toxin B subunit (rCTB) were assessed by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot (ELISPOT) assay. Significant increases in V. cholerae LPS-specific IgA and IgG antibody levels were seen in duodenal extracts on day 30, but the levels decreased to baseline by day 180; plasma V. cholerae LPS-specific IgA levels remained elevated longer. Levels of mucosal CTB antibodies also peaked on day 30, but the increase reached statistical significance only for IgG. A significant correlation was found between the CTB antibodysecreting cell (ASC) response in the circulatory system on day 7 and subsequent CTB-specific IgA levels in duodenal extracts on day 30 and the numbers of CTB-specific IgA ASCs in duodenal tissues on day 180. The proportion (0.07%) of mucosal V. cholerae LPS IgA ASCs peaked on day 30 and remained elevated through day 180 compared to that of HCs (P ‫؍‬ 0.03). These results suggest that protective immunity against V. cholerae is not likely mediated by the constitutive secretion of antibodies at the mucosal surface; our results are consistent with those of other studies that suggest instead that anamnestic immune responses of mucosal lymphocytes may play a major role in protection against cholera.

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“…Another biopsy specimen was used for extraction of lamina propria lymphocytes (LPLs), as described previously (4). Biopsy specimens were washed in PBS and Hank's balanced salts solution (HBSS; H4641; Sigma) and then incubated with EDTA (1 mM) and dithiothreitol (1 mM) with gentle vortexing.…”

Section: Methodsmentioning

confidence: 99%

Vibrio cholerae O1 Infection Induces Proinflammatory CD4⁺T-Cell Responses in Blood and Intestinal Mucosa of Infected Humans

Kuchta

Rahman

Sennott

et al. 2011

Clin Vaccine Immunol

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Vibrio cholerae O1 is a noninvasive enteric pathogen and serves as a model for studies of mucosal immunity. Although symptomatic V. cholerae infection induces durable protection against subsequent disease, vaccination with oral killed whole-cell V. cholerae stimulates less long-lasting protection against cholera. In this study, we demonstrated that cholera induces an early proinflammatory cellular immune response that results in priming of Th1-and Th17-type cytokine responses to ex vivo antigenic stimulation and an increase in the ratio of Th1 to Th2 CD4 ؉ T-cell responses. Comparable priming of Th1 and Th17 responses, with an increased ratio of Th1 to Th2 CD4 ؉ T-cell responses, was not observed in subjects who received two doses of the oral cholera vaccine Dukoral (a whole-cell cholera toxin B subunit containing [WC-CTB] vaccine). These findings suggest that natural V. cholerae infection induces an early, proinflammatory cellular immune response, despite the apparent lack of clinical signs of inflammation. The failure of the WC-CTB vaccine to activate equivalent, CD4؉ T-cell responses is a potential explanation for the shorter duration of protection following immunization with this vaccine. Additional studies are needed to determine whether these early T-cell-mediated events predict the subsequent duration of immunologic memory.Vibrio cholerae causes 3 million to 5 million cases of diarrhea and over 100,000 deaths annually (2). Organisms colonize the epithelial surface of the small intestine and elaborate cholera toxin (CT), an essential virulence factor for all pandemic strains of V. cholerae (30). Because V. cholerae is a prototypical noninvasive pathogen, it serves as a model for the study of mucosal immunity (17).Natural infection with V. cholerae provides greater than 90% protection against subsequent disease for at least 3 years in U.S. volunteer studies (the maximum period studied) and an average of 3 to 8 years on the basis of epidemiological studies in areas of endemicity (5,19,21). The mechanism(s) of protective immunity against cholera is not well understood but has been hypothesized to depend on anamnestic responses of memory B cells (16,25,35). Consistent with this, our group previously demonstrated that V. cholerae protein antigen-specific memory B cells remain detectable in the circulation for over a year following cholera, after circulating antibody levels have returned to baseline levels. In contrast, memory B-cell responses to lipopolysaccharide, a T-cell-independent antigen, were found to decrease more rapidly after infection (16). Such long-lasting memory B cells against V. cholerae protein antigens could play a role in mediating anamnestic responses and protection against subsequent infection.In contrast, a currently licensed cholera vaccine, Dukoral (a whole-cell CT B subunit [WC-CTB] vaccine), consists of killed V. cholerae O1 supplemented with recombinant cholera toxin B subunit (rCTB) and provides over 60% protection. However, protection wanes by 3 years after vaccination, and the vacc...

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Comparison of mucosal B- and T-cell responses inHelicobacter pylori-infected subjects in a developing and a developed country

Cited by 10 publications

References 31 publications

Mucosal Inducible NO Synthase–Producing IgA+ Plasma Cells in Helicobacter pylori–Infected Patients

Mucosal Inducible NO Synthase–Producing IgA+ Plasma Cells in Helicobacter pylori–Infected Patients

Mucosal Immunologic Responses in Cholera Patients in Bangladesh

Vibrio cholerae O1 Infection Induces Proinflammatory CD4⁺T-Cell Responses in Blood and Intestinal Mucosa of Infected Humans

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Comparison of mucosal B- and T-cell responses inHelicobacter pylori-infected subjects in a developing and a developed country

Cited by 10 publications

References 31 publications

Mucosal Inducible NO Synthase–Producing IgA+ Plasma Cells in Helicobacter pylori–Infected Patients

Mucosal Inducible NO Synthase–Producing IgA+ Plasma Cells in Helicobacter pylori–Infected Patients

Mucosal Immunologic Responses in Cholera Patients in Bangladesh

Vibrio cholerae O1 Infection Induces Proinflammatory CD4+T-Cell Responses in Blood and Intestinal Mucosa of Infected Humans

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Vibrio cholerae O1 Infection Induces Proinflammatory CD4⁺T-Cell Responses in Blood and Intestinal Mucosa of Infected Humans