Regulation of Mucosal B Cell Immunoglobulin Secretion by Intestinal Epithelial Cell-Derived Cytokines

Goodrich, Mariam E.; McGee, Dennis W.

doi:10.1006/cyto.1998.0385

Cited by 37 publications

(27 citation statements)

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“…IL-6, IL-10, and transforming growth factor-␤ produced by lymphocytes, phagocytes, and intestinal epithelial cells have been shown to compensate for the absence of classical type 2 helper effects for induction of secretory IgA production (8,15,31), and these alternative B-cell growth and differentiation stimuli may be involved in the induction of T. cruzi-specific secretory IgA responses induced by our type 1 biased immunization protocol. As pointed out above, previous basic immune studies demonstrating that antigen-specific secretory IgA responses can be induced in the absence of type 2 responses have not directly evaluated the relevance of these IgA responses for mucosal protection against infectious pathogens.…”

Section: Discussionmentioning

confidence: 91%

“…Mucosal and systemic protection may require different immune responses. T cells producing interleukin-4 (IL-4), IL-5, and IL-10 (type 2 phenotype) or producing high levels of transforming growth factor-␤ (type 3 phenotype) may be important for induction of secretory immunoglobulin A (IgA) responses protective against mucosal infection (15,32). On the other hand, T cells producing gamma interferon (IFN-␥), tumor necrosis factor alpha, and IL-2 (type 1 phenotype) are clearly protective against systemic intracellular replication of many human pathogens (1,26).…”

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confidence: 99%

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Type 1 Immunity Provides Optimal Protection against Both Mucosal and SystemicTrypanosoma cruziChallenges

Hoft

Eickhoff

2002

Infect Immun

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Chagas' disease results from infection with Trypanosoma cruzi, a protozoan parasite that establishes systemic intracellular infection after mucosal invasion. We hypothesized that ideal vaccines for mucosally invasive, intracellular pathogens like T. cruzi should induce mucosal type 2 immunity for optimal induction of protective secretory immunoglobulin A (IgA) and systemic type 1 immunity protective against intracellular replication. However, differential mucosal and systemic immune memory could be difficult to induce because of reciprocal inhibitory actions between type 1 and type 2 responses. To test our hypotheses, we investigated the protective effects of type 1 and type 2 biased vaccines against mucosal and systemic T. cruzi challenges. Intranasal vaccinations were given with recombinant interleukin-12 (IL-12)-and IL-4-neutralizing antibody (Ab) for type 1 immune bias, or recombinant IL-4 and gamma interferon-neutralizing Ab for type 2 immune bias. Cytokine RNA and protein studies confirmed that highly polarized memory immune responses were induced by our vaccination protocols. Survival after virulent subcutaneous T. cruzi challenge was used to assess systemic protection. Mucosal protection was assessed by measuring the relative inhibition of parasite replication in mucosal tissues early after oral T. cruzi challenge, using both PCR and quantitative culture techniques. As expected, only type 1 responses protected against systemic challenges (P < 0.01). However, contrary to our original hypothesis, type 1 responses optimally protected against mucosal challenges as well (P < 0.05). Type 1 and type 2 biased vaccines induced similar secretory IgA responses. We conclude that future vaccines for T. cruzi and possibly other mucosally invasive, intracellular pathogens should induce both mucosal and systemic type 1 immunity.

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Section: Discussionmentioning

confidence: 91%

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confidence: 99%

Type 1 Immunity Provides Optimal Protection against Both Mucosal and SystemicTrypanosoma cruziChallenges

Hoft

Eickhoff

2002

Infect Immun

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“…PA-DCpep delivered by L. acidophilus elicited a Th1 pattern, indicating that efficient T cell-mediated immunity was critical for the induction of IgA within the small intestine. Interestingly, the higher levels of cytokines such as IL-10 induced in mice vaccinated with L. acidophilus expressing PA-DCpep before challenge with B. anthracis Sterne may play a role in concert with IL-4 and TGF␤ in the induction of IgA and differentiation of B cells (41,42). Additionally, IL-10 may have regulated not only the humoral but also the T cell immune responses in vivo, both of which contributed to a better immunological outcome, possibly leading to the protection of the majority of the animals against Sterne challenge.…”

Section: Discussionmentioning

confidence: 99%

Dendritic cell targeting ofBacillus anthracisprotective antigen expressed byLactobacillus acidophilusprotects mice from lethal challenge

Mohamadzadeh

Duong

Sandwick

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

186

156

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“…Mucosal and systemic protection could require different immune responses. T cells producing interleukin-4 (IL-4), IL-5, and IL-10 (type 2 phenotype), or producing high levels of transforming growth factor ␤ (TGF-␤; type 3 phenotype), induce secretory immunoglobulin A responses protective against mucosal infection (12,36). On the other hand, T cells producing gamma interferon (IFN-␥), tumor necrosis factor alpha, and IL-2 (type 1 phenotype) are clearly protective against systemic intracellular replication of many human pathogens (1,23).…”

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confidence: 99%

Type 1 Immunity Provides Both Optimal Mucosal and Systemic Protection against a Mucosally Invasive, Intracellular Pathogen

Hoft

Eickhoff

2005

Infect Immun

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It has been hypothesized that optimal vaccine immunity against mucosally invasive, intracellular pathogens may require the induction of different types of immune responses in mucosal and systemic lymphoid tissues. Mucosal type 2/3 responses (producing interleukin-4 [IL-4], IL-6 and/or transforming growth factor ␤) could be necessary for optimal induction of protective secretory immunoglobulin A responses. On the other hand, systemic type 1 responses (including gamma interferon [IFN-␥], tumor necrosis factor alpha, and optimal cytotoxic T-cell responses) are likely to be critical for protection against the disseminated intracellular replication that occurs after mucosal invasion. Despite these predictions, we recently found that vaccines inducing highly polarized type 1 immunity in both mucosal and systemic tissues provided optimal mucosal and systemic protection against the protozoan pathogen Trypanosoma cruzi. To further address this important question in a second model system, we now have studied the capacity of knockout mice to develop protective immune memory. T. cruzi infection followed by nifurtimox treatment rescue was used to immunize CD4, CD8, ␤2-microglobulin, inducible nitric oxide synthase (iNOS), IL-12, IFN-␥, and IL-4 knockout mice. Despite the previously demonstrated importance of CD4 ؉ T cells, CD8 ؉ T cells, and nitric oxide for T. cruzi immunity, CD4, CD8, and iNOS knockout mice developed mucosal and systemic protective immunity. However, IL-12, IFN-␥, and ␤2-microglobulin-deficient mice failed to develop mucosal or systemic protection. In contrast, IL-4 knockout mice developed maximal levels of both mucosal and systemic immune protection. These results strongly confirm our earlier conclusion from studies with polarizing vaccination protocols that type 1 immunity provides optimal mucosal and systemic protection against a mucosally invasive, intracellular pathogen.

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Regulation of Mucosal B Cell Immunoglobulin Secretion by Intestinal Epithelial Cell-Derived Cytokines

Cited by 37 publications

References 0 publications

Type 1 Immunity Provides Optimal Protection against Both Mucosal and SystemicTrypanosoma cruziChallenges

Type 1 Immunity Provides Optimal Protection against Both Mucosal and SystemicTrypanosoma cruziChallenges

Dendritic cell targeting ofBacillus anthracisprotective antigen expressed byLactobacillus acidophilusprotects mice from lethal challenge

Type 1 Immunity Provides Both Optimal Mucosal and Systemic Protection against a Mucosally Invasive, Intracellular Pathogen

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