Distribution of Primed T Cells and Antigen-Loaded Antigen Presenting Cells Following Intranasal Immunization in Mice

Ciabattini, Annalisa; Pettini, Elena; Fiorino, Fabio; Prota, Gennaro; Pozzi, Gianni; Medaglini, Donata

doi:10.1371/journal.pone.0019346

Cited by 39 publications

(44 citation statements)

References 47 publications

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“…Although early DC antigen presenting activity in the draining CLN was described for i. n. immunization experiments with viral antigens [28], our adjuvant candidate c-di-AMP alone did not notably induce T cell stimulatory molecules on APCs of the CLN after 24 h. The more pronounced DC activation was observed in the NALT, the lymphoid tissue directly associated with the site of administration, and also in the MLN. The early DC response in the MLN is in line with several studies reporting a similar observation upon i. n. immunization with model antigens and adjuvants [29]–[31] as well as upon i. n. infection with influenza virus [32]. We also demonstrated that murine DCs and MΦs/monocytes/granulocytes respond to in vivo administration of c-di-AMP by the up-regulation of IFN-β expression (Figure 4A).…”

Section: Discussionsupporting

confidence: 91%

The Mucosal Adjuvant Cyclic di-AMP Exerts Immune Stimulatory Effects on Dendritic Cells and Macrophages

et al. 2014

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The cyclic di-nucleotide bis-(3′,5′)-cyclic dimeric adenosine monophosphate (c-di-AMP) is a candidate mucosal adjuvant with proven efficacy in preclinical models. It was shown to promote specific humoral and cellular immune responses following mucosal administration. To date, there is only fragmentary knowledge on the cellular and molecular mode of action of c-di-AMP. Here, we report on the identification of dendritic cells and macrophages as target cells of c-di-AMP. We show that c-di-AMP induces the cell surface up-regulation of T cell co-stimulatory molecules as well as the production of interferon-β. Those responses were characterized by in vitro experiments with murine and human immune cells and in vivo studies in mice. Analyses of dendritic cell subsets revealed conventional dendritic cells as principal responders to stimulation by c-di-AMP. We discuss the impact of the reported antigen presenting cell activation on the previously observed adjuvant effects of c-di-AMP in mouse immunization studies.

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Section: Discussionsupporting

confidence: 91%

The Mucosal Adjuvant Cyclic di-AMP Exerts Immune Stimulatory Effects on Dendritic Cells and Macrophages

et al. 2014

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“…This was unique to this population and not observed on Foxp3 + Tregs or non-Tregs. Intranasal vaccination has also been described to elicit migration of antigen-specific T cells to the MLN that can protect against intestinal pathogens 50, 51 , indicating that tissue-specific imprinting is a flexible and cell-type specific process. Understanding how to manipulate this homing potential has major implications for vaccine and immunotherapy design.…”

Section: Discussionmentioning

confidence: 99%

Epicutaneous immunotherapy induces gastrointestinal LAP + regulatory T cells and prevents food-induced anaphylaxis

Tordesillas

Mondoulet

Blázquez

et al. 2017

Journal of Allergy and Clinical Immunology

137

122

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Background The attempt to induce oral tolerance as a treatment for food allergy has been hampered by a lack of sustained clinical protection. Immunotherapy by non-oral routes, such as the skin, may be more effective for the development of maintained tolerance to food allergens. Objective To determine the efficacy and mechanism of tolerance induced by epicutaneous immunotherapy in a model of food-induced anaphylaxis. Methods C3H/HeJ mice were sensitized to ovalbumin (OVA) orally or through the skin and treated with EPIT using OVA-Viaskin® patches or OIT using OVA. Mice were orally challenged with OVA to induce anaphylaxis. Antigen-specific Treg induction was assessed by flow cytometry using a transgenic T cell transfer model. Results Using an adjuvant-free model of food allergy generated by epicutaneous sensitization and reactions triggered by oral allergen challenge, we found that epicutaneous immunotherapy induced sustained protection against anaphylaxis. We show that the gastrointestinal tract is deficient in de novo generation of Tregs in allergic mice. This defect was tissue-specific, and epicutaneous application of antigen generated a population of gastrointestinal-homing LAP+Foxp3− Tregs. The mechanism of protection was found to be a novel pathway of direct TGF-β-dependent Treg suppression of mast cell activation, in the absence of modulation of T or B cell responses. Conclusions Our data highlights the immune communication between skin and gastrointestinal tract, and identifies novel mechanisms by which epicutaneous tolerance can suppress food-induced anaphylaxis.

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“…Ciabattini et al showed that following i.n. immunization of mice, antigen-specific proliferating T cells were observed in the distal lymph nodes and the spleen (28). Importantly, Ruane et al reported that lung dendritic cells targeted by i.n.…”

Section: Discussionmentioning

confidence: 99%

Intranasal Administration of Mycobacterium bovis BCG Induces Superior Protection against Aerosol Infection with Mycobacterium tuberculosis in Mice

Derrick

Kolibab

Yang

et al. 2014

Clin Vaccine Immunol

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Despite the widespread use of Mycobacterium bovis BCG, the only licensed vaccine against tuberculosis (TB), TB remains a global epidemic. To assess whether more direct targeting of the lung mucosa by respiratory immunization would enhance the potency and longevity of BCG-induced anti-TB protective immunity, the long-term impact of intranasal (i.n.) BCG vaccination was compared to conventional subcutaneous (s.c.) immunization by using a mouse model of pulmonary tuberculosis. Although significantly improved protection in the lung was seen at early time points (2 and 4 months postvaccination) in i.n. BCG-immunized mice, no differences in pulmonary protection were seen 8 and 10 months postvaccination. In contrast, in all of the study periods, i.n. BCG vaccination induced significantly elevated protective splenic responses relative to s.c. immunization. At five of nine time points, we observed a splenic protective response exceeding 1.9 log 10 protection relative to the s.c. route. Furthermore, higher frequencies of CD4 T cells expressing gamma interferon (IFN-␥) and IFN-␥/tumor necrosis factor alpha, as well as CD8 T cells expressing IFN-␥, were detected in the spleens of i.n. vaccinated mice. Using PCR arrays, significantly elevated levels of IFN-␥, interleukin-9 (IL-9), IL-11, and IL-21 expression were also seen in the spleen at 8 months after respiratory BCG immunization. Overall, while i.n. BCG vaccination provided short-term enhancement of protection in the lung relative to s.c. immunization, potent and extremely persistent splenic protective responses were seen for at least 10 months following respiratory immunization. More than a century after Robert Koch first described how to culture tubercle bacilli, Mycobacterium tuberculosis remains one of the most successful human pathogens and a major global public health threat. According to the recent WHO global tuberculosis (TB) report, 1.3 million people died from TB in 2012 and 8.6 million new cases of the disease were detected (1). Next to HIV, TB is the most important cause of death from an infectious agent in low-income countries. Recommended by the WHO, live, attenuated Mycobacterium bovis BCG is the only TB vaccine approved for human use, being administered intradermally (i.d.) to more than 70% of children worldwide (2). Although i.d. BCG vaccination has been shown to be effective in preventing severe forms of extrapulmonary TB, its ability to protect against pulmonary TB in controlled clinical trials has been highly variable (0 to 80%) (3-5). Importantly, it has been estimated that i.d. BCG immunization prevents only about 5% of vaccine-preventable deaths (6). Clearly, novel, more effective TB immunization strategies are needed.Despite 9 decades of BCG vaccine use, the optimal vaccine dose and route of administration have not been fully defined. Since TB is primarily a pulmonary infection, respiratory BCG immunization has long been considered an attractive alternative to i.d. vaccination. With immune lymphoid mucosal and bronchial tissues being targeted by r...

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Distribution of Primed T Cells and Antigen-Loaded Antigen Presenting Cells Following Intranasal Immunization in Mice

Cited by 39 publications

References 47 publications

The Mucosal Adjuvant Cyclic di-AMP Exerts Immune Stimulatory Effects on Dendritic Cells and Macrophages

The Mucosal Adjuvant Cyclic di-AMP Exerts Immune Stimulatory Effects on Dendritic Cells and Macrophages

Epicutaneous immunotherapy induces gastrointestinal LAP + regulatory T cells and prevents food-induced anaphylaxis

Intranasal Administration of Mycobacterium bovis BCG Induces Superior Protection against Aerosol Infection with Mycobacterium tuberculosis in Mice

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