Long-term systemic and mucosal antibody responses measured in BALB/c mice following intranasal challenge with viable enterotoxigenic<i>Escherichia coli</i>

Byrd, Wyatt; Cassels, Frederick J.

doi:10.1111/j.1574-695x.2005.00039.x

Cited by 5 publications

(5 citation statements)

References 19 publications

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“…The significant association between increased fecal IL-4 levels and decreased ETEC infection durations is consistent with the protective role of an upregulated Th2 cytokine response against ETEC infections (5,6,37). An anti-enterotoxin (anti-LT) intestinal IgA response upregulated by Th2 cytokines is important in resolving ETEC infection and so may be mediating this association (11).…”

Section: Discussionsupporting

confidence: 74%

Associations between Mucosal Innate and Adaptive Immune Responses and Resolution of Diarrheal Pathogen Infections

et al. 2010

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The identification of immune response mechanisms that contribute to the control of diarrheal disease in developing countries remains an important priority. We addressed the role of fecal chemokines and cytokines in the resolution of diarrheal Escherichia coli and Giardia lamblia infections. Stools collected from 127 Mexican children 5 to 15 months of age enrolled in a randomized, double-blind, placebo-controlled, vitamin A supplementation trial were screened for enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC), and Giardia lamblia. Fecal concentrations of tumor necrosis factor alpha (TNF-␣), monocyte chemoattractant protein-1 (MCP-1), interleukin-4 (IL-4), IL-5, IL-6, IL-8, IL-10, and interferon-␥ (IFN-␥) were determined. Hazard models incorporating cytokine variables were fit to durations of asymptomatic and symptomatic pathogen infections, controlling for treatment group. Increased levels of TNF-␣ and IL-6 were associated with decreased durations of EPEC infection and increased ETEC durations. Increased IL-4 and IFN-␥ levels were associated with decreased and increased durations, respectively, of both EPEC and ETEC infections. Increased IL-10 levels were associated with increased and decreased durations of asymptomatic and symptomatic EPEC infections, respectively, and increased durations of both asymptomatic and symptomatic ETEC infections. Increased levels of MCP-1, IFN-␥, IL-4, and IL-5 were associated with increased G. lamblia infection duration, while increased IL-8 levels were associated with decreased durations. Differences in proinflammatory and Treg cytokine levels are associated with differences in the resolution of inflammatory and noninflammatory pathogen infections.Pediatric diarrheal disease continues to be an important health problem in developing countries, with the disabilityadjusted life year (DALY) for this disease estimated to be approximately 100 million, Ͼ95% of which is due to mortality (36). A broad range of gastrointestinal pathogens cause diarrhea among young children in these settings. Diarrheagenic Escherichia coli pathotypes (DEPs) represent a leading bacterial cause of diarrhea, with enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC) representing the most important pathogens of this group (7, 41). The disease burden due to such gastrointestinal parasites as Giardia lamblia also continues to be an important health problem in countries such as Mexico (31).We have addressed the efficacy of vitamin A supplementation in reducing the burden of pathogen-specific diarrhea by carrying out a randomized, placebo-controlled, double-blind trial among children living in peri-urban areas of Mexico City. Supplementation in this trial was associated with pathogenspecific effects on the fecal innate and adaptive cytokine responses and with divergent pathogen-specific clinical outcomes (30, 32). We now want to understand how the effect of vitamin A on these cytokine responses is associated with pathogenspecific outcomes.Recent research has reported that distin...

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Section: Discussionsupporting

confidence: 74%

Associations between Mucosal Innate and Adaptive Immune Responses and Resolution of Diarrheal Pathogen Infections

et al. 2010

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“…In our investigation, 10 9 CFU of ETEC H10407 resulted in 100% mortality in the unimmunised mice within 24 h. Similar observations were reported [41,42]. In contrast, a lower dose of 10 8 CFU also resulted in 100% mortality in mice [38][39][40]. On the other hand, in this study, 10 8 CFU caused only 33.33% mortality.…”

Section: Discussionsupporting

confidence: 88%

“…The BALB/c mouse is among the most widely used inbred animal models used in biomedical research and is particularly utilized in immunology and infectious disease research [37]. Most researchers have used BALB/c mice for the development of an ETEC vaccine and challenge studies, as BALB/c mice are susceptible to ETEC infection [38][39][40][41][42]. In mice, a lethal challenge dose of 10 8 CFU/mL of ETEC H10407 [38][39][40] or 10 9 CFU/mL [41,42] were reported.…”

Section: Discussionmentioning

confidence: 99%

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Dual-Use Vaccine for Diarrhoeal Diseases: Cross-Protective Immunogenicity of a Cold-Chain-Free, Live-Attenuated, Oral Cholera Vaccine against Enterotoxigenic Escherichia coli (ETEC) Challenge in BALB/c Mice

et al. 2022

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In low- and middle-income countries, diarrhoeal diseases are the second most common cause of mortality in children, mainly caused by enterotoxin-producing bacteria, such as Shigella, Vibrio, Salmonella, and Escherichia coli. Cholera and traveller’s diarrhoea are caused by Vibrio cholerae (O1 and O139 serogroups) and enterotoxigenic Escherichia coli (ETEC), respectively. The cholera toxin (CT) produced by V. cholerae and the heat-labile enterotoxin (LT) of ETEC are closely related by structure, function, and the immunological response to them. There is no exclusive vaccine for ETEC; however, cholera vaccines based on the CT-B component elicit a short-term cross-protection against ETEC infection. In this context, the cross-protective efficacy of MyCholTM, a prototype cold-chain-free, live-attenuated, oral cholera vaccine against V. cholerae O139 was evaluated in BALB/c mice. The 100% lethal dose (LD100) of 109 CFU/mL of the ETEC H10407 strain was used for the challenge studies. The mice immunised with MyChol™ survived the challenge by producing anti-CT antibodies, which cross-neutralised the LT toxin with no body weight loss and no sign of diarrhoea. Compared to unimmunised mice, the immunised mice elicited the neutralising antitoxin that markedly decreased ETEC colonisation and fluid accumulation caused by ETEC H10407 in the intestines. The immunised mice recorded higher antibody titres, including anti-CT IgG, anti-LT IgG, anti-CT-B IgG, and anti-LTB IgG. Only a two-fold rise in anti-CT/CT-B/LT/LT-B IgA was recorded in serum samples from immunised mice. No bactericidal antibodies against ETEC H10407 were detected. This investigation demonstrates the safety, immunogenicity, and cross-protective efficacy of MyCholTM against the ETEC H10407 challenge in BALB/c mice.

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“…The production of all four IgG subclasses has been reported after animals have been challenged with widely varying antigens including DNA vaccines, 32 recombinant Ascaris suum antigens, 33 recombinant Plasmodium antigens 34 and bacterial adhesins, 35 as well as after infection with bacteria 36 and a range of viruses 37 , 38 , 39 . The four subclasses have also been reported in response to T‐independent antigens.…”

Section: The Mouse Igg Response Usually Involves All Subclassesmentioning

confidence: 98%

IgG subclass co‐expression brings harmony to the quartet model of murine IgG function

2016

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A model of murine IgG function is presented in which the co-expression of the IgG subclasses is a central feature, class switching occurs before the commencement of somatic hypermutation, and there is little switching between subclasses. It is named the quartet model to emphasize the harmony that comes from the simultaneous presence of the four subclasses. In this model, IgG3 and IgG2b antibodies are particularly important early in the response, when T-cell help may be limiting. IgG3 initiates inflammation through complement fixation, whereas IgG2b provides early FcγR-mediated effector functions. As T-cell help strengthens, IgG2a antibodies increase the power of the response, whereas IgG1 production helps limit the inflammatory drive and limits immunopathology. The model highlights the fact that murine IgG subclasses function quite differently to human IgG subclasses. This allows them to serve the special immunological needs of a species that is vulnerable because of its small size.

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Long-term systemic and mucosal antibody responses measured in BALB/c mice following intranasal challenge with viable enterotoxigenicEscherichia coli

Cited by 5 publications

References 19 publications

Associations between Mucosal Innate and Adaptive Immune Responses and Resolution of Diarrheal Pathogen Infections

Associations between Mucosal Innate and Adaptive Immune Responses and Resolution of Diarrheal Pathogen Infections

Dual-Use Vaccine for Diarrhoeal Diseases: Cross-Protective Immunogenicity of a Cold-Chain-Free, Live-Attenuated, Oral Cholera Vaccine against Enterotoxigenic Escherichia coli (ETEC) Challenge in BALB/c Mice

IgG subclass co‐expression brings harmony to the quartet model of murine IgG function

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