Mucosally Induced Immunoglobulin E-Associated Inflammation in the Respiratory Tract

Simecka, Jerry W.; Jackson, Raymond J.; Kanazawa, Hiroshi; McGhee, Jerry R.

doi:10.1128/iai.68.2.672-679.2000

Cited by 41 publications

(40 citation statements)

References 29 publications

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“…Our results show robust expression of IFN-g, IL-2 and TNF-a in CD4 1 T cells after immunization with HEL and CT, whereas IL-4 and IL-5 were not detectable, which is in contrast with previous reports that indicated a Th2 cytokine response after ear immunization [10,11]; this also argues against the occurrence of dominant Th2 responses toward antigens that are coadministered with CT in mucosae [16,17]. In the skin, both Th1 and Th2 cytokines have been reported following immunization with OVA and CT [24].…”

Section: Discussioncontrasting

confidence: 99%

“…It has been reported that LCs remain in the epidermis for 48 h, even in the presence of Th1-polarizing adjuvants [7]. In our experiments, 24 h after CT or CTB inoculation in the ear, the number of LCs in the epidermis was reduced, suggesting that LCs could be mobilized from the dermis at this time point in the presence of strong adjuvants such as CT.Our results show robust expression of IFN-g, IL-2 and TNF-a in CD4 1 T cells after immunization with HEL and CT, whereas IL-4 and IL-5 were not detectable, which is in contrast with previous reports that indicated a Th2 cytokine response after ear immunization [10,11]; this also argues against the occurrence of dominant Th2 responses toward antigens that are coadministered with CT in mucosae [16,17]. In the skin, both Th1 and Th2 cytokines have been reported following immunization with OVA and CT [24].…”

contrasting

confidence: 92%

“…When administered in the mucosa, CT can elicit a Th2-type response that is based on the production of IL-4, IL-5 and IL-10 but virtually no IFN-g [16,17]. However, a mixed Th1/Th2 response that produces both IFN-g and IL-4 has also been observed [18], and the administration of ovalbumin (OVA) in combination with CT elicits a dominant Th17 response following intranasal immunization [19].…”

Section: Introductionmentioning

confidence: 99%

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Intradermal immunization in the ear with cholera toxin and its non‐toxic β subunit promotes efficient Th1 and Th17 differentiation dependent on migrating DCs

et al. 2011

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The nature of CD4 1 T-cell responses after skin immunization and the role of migrating DCs in the presence of adjuvants in the elicited response are interesting issues to be investigated. Here, we evaluated the priming of CD4 1 T cells following ear immunization with low doses of model antigens in combination with either cholera toxin (CT) or the non-toxic b CT subunit (CTB) as an adjuvant. Following immunization with CT, we found efficient antigen presentation that is reflected in the production of IFN-c and IL-17 by CD4 1 T cells over IL-4 or IL-5 production. The CTB-induced activation of DCs in the ear occurred without visible inflammation, which reflects a similar type of CD4 1 T-cell differentiation. In both cases, the elicited response was dependent on the presence of migrating skin cells. Remarkably, immunization with CT or with CTB led to the induction of a delayed-type hypersensitivity (DTH) response in the ear. The DTH response that was induced by CT immunization was dependent on IL-17 and partially dependent on IFN-c activity. These results indicate that both CT and CTB induce an efficient CD4 1 T-cell response to a co-administered antigen following ear immunization that is dependent on migrating DCs.Key words: DCs . Migrating DCs . Skin immunization Supporting Information available online IntroductionThe skin is the first line of defense against microbial pathogens. There is supporting evidence that DCs are crucial for the initiation, polarization and control of the adaptive immune response [1,2]. Efficient immunosurveillance in the skin is based upon the continuous traffic of cells from the skin to the draining lymph nodes. Although Langerhans cells (LCs) have been shown to be potent APCs in vitro [3], in vivo approaches have produced conflicting data regarding their role in T-cell priming [4,5]. Dermal DCs are also migrating DCs that colonize lymph nodes more rapidly than LCs [6,7], and different roles for skin DC subsets in T-cell priming have been reported [7][8][9]. Skin immunization has yielded controversial data, with some reports supporting a Th2-type response [10,11] and others a Th1-type response [12,13]. IL-17-producing CD4 1 T cells (Th17) have also been found after skin immunization [13,14]. 2894Cholera toxin (CT) has a strong adjuvant effect [15]. When administered in the mucosa, CT can elicit a Th2-type response that is based on the production of IL-4, IL-5 and IL-10 but virtually no 17]. However, a mixed Th1/Th2 response that produces both IFN-g and IL-4 has also been observed [18], and the administration of ovalbumin (OVA) in combination with CT elicits a dominant Th17 response following intranasal immunization [19]. This dominance of IL-17 was also observed in response to the CT b subunit (CTB). Although the precise mechanism for the adjuvant effect of CT is not completely understood, it appears that CTB targets DCs in vivo by binding to the cell membrane ganglioside GM1 [20]; moreover, the CT a subunit (CTA) triggers the PKA-mediated induction of cAMP, which plays a critical role ...

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Section: Discussioncontrasting

confidence: 99%

contrasting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Intradermal immunization in the ear with cholera toxin and its non‐toxic β subunit promotes efficient Th1 and Th17 differentiation dependent on migrating DCs

et al. 2011

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“…44 To date, no animal model has addressed how oral and nasal sensitization to peanut affects allergic manifestations and, more specifically, the cellular and molecular events after nasal challenge with peanut or unrelated antigens. We hypothesized that mucosal sensitization in the presence of CT, a mucosal adjuvant that promotes IgE Ab and Th2-type responses, 34,45,46 could aid the development of mouse models of peanut allergy by either oral or nasal sensitization. We found that oral sensitization of mice induced higher levels of peanut-specific plasma IgE Ab responses and higher lung eosinophilia after nasal challenge with peanut.…”

Section: Discussionmentioning

confidence: 99%

Oral and Nasal Sensitization Promote Distinct Immune Responses and Lung Reactivity in a Mouse Model of Peanut Allergy

Fischer

McGhee

et al. 2005

The American Journal of Pathology

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Despite structural and functional differences between the initial sites of contact with allergens in the gastrointestinal and nasal tracts, few animal models have examined the influence of the mucosal routes of sensitization on host reactivity to food or environmental antigens. We compared the oral and nasal routes of peanut sensitization for the development of a mouse model of allergy. Mice were sensitized by administration of peanut proteins in the presence of cholera toxin as adjuvant. Antibody and cytokine responses were characterized, as well as airway reactivity to nasal challenge with peanut or unrelated antigens. Oral sensitization promoted higher levels of IgE, but lower IgG responses, than nasal sensitization. Both orally and nasally sensitized mice experienced airway hyperreactivity on nasal peanut challenge. The peanut challenge also induced lung eosinophilia and type 2 helper T-cell-type cytokines in orally sensitized mice. In contrast, peanut challenge in nasally sensitized mice promoted neutrophilia and higher levels of The prevalence of peanut allergy has doubled in the last decade, and it now affects more than 3 million individuals in the United States.

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“…Concerns have been raised as to potential problems that could be encountered with the use of cholera and heatlabile bacterial toxins and toxoids when administered intranasally (van Ginkel et al, 2000). Involvement of nasal and respiratory surfaces with these adjuvants has the potential of inducing adverse inflammatory responses (Simecka et al, 2000;van Ginkel et al, 2000). Total serum IgE was elevated in mice intranasally administered mLT as a mucosal adjuvant, with no elevated levels of total serum IgE measured in mice intranasally administered native CS3 or the CS3-PLGA microspheres.…”

Section: Discussionmentioning

confidence: 99%

The encapsulation of enterotoxigenic Escherichia coli colonization factor CS3 in biodegradable microspheres enhances the murine antibody response following intranasal administration

Byrd

Cassels

2006

Microbiology

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The aim of this study was to measure serum and mucosal antibody responses following intranasal administration of biodegradable poly(DL-lactide-co-glycolide) (PLGA) microspheres loaded with the CS3 colonization factor isolated from enterotoxigenic Escherichia coli (ETEC). The response was compared against that measured in mice similarly administered the native CS3 antigen and in mice co-administered, along with the CS3 antigen, a known mucosal adjuvant, the R192G mutant heat-labile enterotoxin (mLT). The integrity of the CS3 antigen released from the microspheres was maintained as determined by SDS-PAGE and immunoblotting. Native CS3 induced serum and mucosal (bronchoalveolar, small intestinal and faecal) IgG and IgA responses. The co-administration of the mLT mucosal adjuvant significantly enhanced (P<0?001) serum and mucosal antibody responses to the CS3 protein. Likewise, the CS3-loaded PLGA microspheres induced significantly greater (P<0?001) serum and mucosal antibody responses than native CS3, as well as inducing antibody responses superior to those of the CS3 plus mLT formulation. Following administration of CS3 plus mLT, the mice became distressed (loss of activity, increased huddling, ruffled fur), a situation not seen following administration of the CS3-loaded PLGA microspheres. The results in this trial show that the CS3-loaded PLGA microspheres when administered intranasally to mice caused no observable distress to the mice and significantly (P<0?001) enhanced the immunogenicity of the CS3 protein. INTRODUCTIONEnterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhoea in children in developing countries, with an estimated 800 000 deaths among those under the age of 5 years (Gaastra & Svennerholm, 1996). ETEC is also an agent of diarrhoea in travellers to high-risk areas (Black, 1990), and is of critical concern for military units assigned to these areas of operation (Hyams et al., 1991). A safe and effective vaccine directed against ETEC would be of considerable public health benefit. However, at present, no licensed ETEC vaccine is available for at-risk individuals.Administering antigen directly to the mucosa-associated lymphoid tissue (MALT), such as the nasal mucosa, can act to induce both local and systemic specific immune responses (Eyles et al., 1998a). This is particularly important considering that most pathogens enter the body via mucosal surfaces, and protection against such organisms most often requires local production of antibodies, most importantly, secretory IgA (sIgA) (Eyles et al., 1998b). Native antigens can be weak immunogens when administered to mucosal surfaces as a result of adverse conditions and/or inadequate absorption (Eyles et al., 1998b). However, mucosal delivery vehicles, such as PLGA microspheres, can act to protect antigens as well as increasing their absorption, thus enhancing the immunogenicity of the antigens (Byrd et al., 2005;Eldridge et al., 1991b).In this study, the immune response in BALB/c mice intranasally administered CS3-loaded poly(DL-lactide-c...

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Mucosally Induced Immunoglobulin E-Associated Inflammation in the Respiratory Tract

Cited by 41 publications

References 29 publications

Intradermal immunization in the ear with cholera toxin and its non‐toxic β subunit promotes efficient Th1 and Th17 differentiation dependent on migrating DCs

Intradermal immunization in the ear with cholera toxin and its non‐toxic β subunit promotes efficient Th1 and Th17 differentiation dependent on migrating DCs

Oral and Nasal Sensitization Promote Distinct Immune Responses and Lung Reactivity in a Mouse Model of Peanut Allergy

The encapsulation of enterotoxigenic Escherichia coli colonization factor CS3 in biodegradable microspheres enhances the murine antibody response following intranasal administration

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