Background: Recent data suggested that non-gastrointestinal exposure can lead to sensitisation to food allergens. We thus assessed the immune impact of respiratory or cutaneous exposure to peanut proteins on non-altered epithelium and investigated the effect of such pre-exposure on subsequent oral administration of peanut. Methods: BALB/cJ mice were exposed to purified Ara h 1 or to a non-defatted roasted peanut extract (PE) by simple deposit of allergens solutions on non-altered skin or in the nostrils. Exposures were performed 6 times at weekly intervals. Pre-exposed mice then received intra-gastric administrations of PE alone or in the presence of the Th2 mucosal adjuvant cholera toxin (CT). The specific humoral and cellular immune response was assessed throughout the protocol. Results: Both cutaneous and respiratory exposures led to the production of specific IgG1. Local and systemic IL-5 and IL-13 production were also evidenced, demonstrating activation of specific Th2 cells. This effect was dose-dependent and most efficient via the respiratory route. Moreover, these pre-exposures led to the production of specific IgE antibodies after gavage with PE, whatever the presence of CT. Conclusions: Cutaneous or respiratory exposures to peanut induce Th2 priming in mice. Moreover, pre-exposures promote further sensitisation via the oral route without the use of CT; this proposes a new adjuvant-free experimental model of sensitisation to food that may reflect a realistic exposure pattern in infants. These results also suggest that non-gastrointestinal peanut exposure should be minimised in high-risk infants, even those with non-altered skin, to potentially reduce allergic sensitisation to this major food allergen.

Du Toit G, Katz Y, Sasieni P, Mesher D, Maleki SJ, Fisher HR, Fox AT, Turcanu V, Amir T, Zadik-Mnuhin G, Cohen A, Livne I, Lack G: Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol 2008;122:984-991.
Fox AT, Sasieni P, du Toit G, Syed H, Lack G: Household peanut consumption as a risk factor for the development of peanut allergy. J Allergy Clin Immunol 2009;123:417-423.
Lack G, Fox D, Northstone K, Golding J; Team ALSoPaCS: Factors associated with the development of peanut allergy in childhood. N Engl J Med 2003;348:977-985.
Brown SJ, Asai Y, Cordell HJ, Campbell LE, Zhao Y, Liao H, Northstone K, Henderson J, Alizadehfar R, Ben-Shoshan M, Morgan K, Roberts G, Masthoff LJ, Pasmans SG, van den Akker PC, Wijmenga C, Hourihane JO, Palmer CN, Lack G, Clarke A, Hull PR, Irvine AD, McLean WH: Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol 2011;127:661-667.
Ramirez DA, Bahna SL: Food hypersensitivity by inhalation. Clin Mol Allergy 2009;7:4.
Sicherer SH, Furlong TJ, DeSimone J, Sampson HA: Self-reported allergic reactions to peanut on commercial airliners. J Allergy Clin Immunol 1999;104:186-189.
Alday E, Curiel G, Lopez-Gil MJ, Carreño D, Moneo I: Occupational hypersensitivity to sesame seeds. Allergy 1996;51:69-70.
Jacobs JH, Meijster T, Meijer E, Suarthana E, Heederik D: Wheat allergen exposure and the prevalence of work-related sensitization and allergy in bakery workers. Allergy 2008;63:1597-1604.
Kondo H, Ichikawa Y, Imokawa G: Percutaneous sensitization with allergens through barrier-disrupted skin elicits a Th2-dominant cytokine response. Eur J Immunol 1998;28:769-779.
Vaali K, Puumalainen TJ, Lehto M, Wolff H, Rita H, Alenius H, Palosuo T: Murine model of food allergy after epicutaneous sensitization: role of mucosal mast cell protease-1. Scand J Gastroenterol 2006;41:1405-1413.
Hsieh KY, Tsai CC, Wu CH, Lin RH: Epicutaneous exposure to protein antigen and food allergy. Clin Exp Allergy 2003;33:1067-1075.
Strid J, Hourihane J, Kimber I, Callard R, Strobel S: Disruption of the stratum corneum allows potent epicutaneous immunization with protein antigens resulting in a dominant systemic Th2 response. Eur J Immunol 2004;34:2100-2109.
Wang LF, Lin JY, Hsieh KH, Lin RH: Epicutaneous exposure of protein antigen induces a predominant Th2-like response with high IgE production in mice. J Immunol 1996;156:4077-4082.
Nelde A, Teufel M, Hahn C, Duschl A, Sebald W, Bröcker EB, Grunewald SM: The impact of the route and frequency of antigen exposure on the IgE response in allergy. Int Arch Allergy Immunol 2001;124:461-469.
Parvataneni S, Gonipeta B, Tempelman RJ, Gangur V: Development of an adjuvant-free cashew nut allergy mouse model. Int Arch Allergy Immunol 2009;149:299-304.
Dunkin D, Berin MC, Mayer L: Allergic sensitization can be induced via multiple physiologic routes in an adjuvant-dependent manner. J Allergy Clin Immunol 2011;128:1251-1258.e1252.
Poms RE, Capelletti C, Anklam E: Effect of roasting history and buffer composition on peanut protein extraction efficiency. Mol Nutr Food Res 2004;48:459-464.
de Jong EC, Van Zijverden M, Spanhaak S, Koppelman SJ, Pellegrom H, Penninks AH: Identification and partial characterization of multiple major allergens in peanut proteins. Clin Exp Allergy 1998;28:743-751.
Mondoulet L, Paty E, Drumare MF, Ah-Leung S, Scheinmann P, Willemot RM, Wal JM, Bernard H: Influence of thermal processing on the allergenicity of peanut proteins. J Agric Food Chem 2005;53:4547-4553.
Bernard H, Drumare MF, Guillon B, Paty E, Scheinmann P, Wal JM: Immunochemical characterisation of structure and allergenicity of peanut 2S albumins using different formats of immunoassays. Anal Bioanal Chem 2009;395:139-146.
Clement G, Boquet D, Mondoulet L, Lamourette P, Bernard H, Wal JM: Expression in Escherichia coli and disulfide bridge mapping of PSC33, an allergenic 2S albumin from peanut. Protein Expr Purif 2005;44:110-120.
Bernard H, Ah-Leung S, Drumare MF, Feraudet-Tarisse C, Verhasselt V, Wal JM, Créminon C, Adel-Patient K: Peanut allergens are rapidly transferred in human breast milk and can prevent sensitization in mice. Allergy 2014;69:888-897.
Adel-Patient K, Bernard H, Ah-Leung S, Créminon C, Wal JM: Peanut- and cow's milk-specific IgE, Th2 cells and local anaphylactic reaction are induced in Balb/c mice orally sensitized with cholera toxin. Allergy 2005;60:658-664.
Adel-Patient K, Wavrin S, Bernard H, Meziti N, Ah-Leung S, Wal JM: Oral tolerance and Treg cells are induced in Balb/c mice after gavage with bovine β-lactoglobulin. Allergy 2011;66:1312-1321.
Adel-Patient K, Créminon C, Bernard H, Clément G, Négroni L, Frobert Y, Grassi J, Wal JM, Chatel JM: Evaluation of a high IgE-responder mouse model of allergy to bovine beta-lactoglobulin (BLG): Development of sandwich immunoassays for total and allergen-specific IgE, IgG1 and IgG2a in BLG-sensitized mice. J Immunol Methods 2000;235:21-32.
Grassi J, Frobert Y, Pradelles P, Chercuitte F, Gruaz D, Dayer JM, Poubelle PE: Production of monoclonal antibodies against interleukin-1 alpha and -1 beta. Development of two enzyme immunometric assays (EIA) using acetylcholinesterase and their application to biological media. J Immunol Methods 1989;123:193-210.
Strid J, Hourihane J, Kimber I, Callard R, Strobel S: Epicutaneous exposure to peanut protein prevents oral tolerance and enhances allergic sensitization. Clin Exp Allergy 2005;35:757-766.
Sicherer SH, Leung DY: Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2012. J Allergy Clin Immunol 2013;131:55-66.
Chan SM, Turcanu V, Stephens AC, Fox AT, Grieve AP, Lack G: Cutaneous lymphocyte antigen and α4β7 T-lymphocyte responses are associated with peanut allergy and tolerance in children. Allergy 2012;67:336-342.
Oyoshi MK, Murphy GF, Geha RS: Filaggrin-deficient mice exhibit Th17-dominated skin inflammation and permissiveness to epicutaneous sensitization with protein antigen. J Allergy Clin Immunol 2009;124:485-493, 493.e481.
Gonipeta B, Parvataneni S, Paruchuri P, Gangur V: Long-term characteristics of hazelnut allergy in an adjuvant-free mouse model. Int Arch Allergy Immunol 2010;152:219-225.
Navuluri L, Parvataneni S, Hassan H, Birmingham NP, Kelly C, Gangur V: Allergic and anaphylactic response to sesame seeds in mice: identification of Ses i 3 and basic subunit of 11s globulins as allergens. Int Arch Allergy Immunol 2006;140:270-276.
Brough HA, Makinson K, Penagos M, Maleki SJ, Cheng H, Douiri A, Stephens AC, Turcanu V, Lack G: Distribution of peanut protein in the home environment. J Allergy Clin Immunol 2013;132:623-629.
Lehto M, Koivuluhta M, Wang G, Amghaiab I, Majuri ML, Savolainen K, Turjanmaa K, Wolff H, Reunala T, Lauerma A, Palosuo T, Alenius H: Epicutaneous natural rubber latex sensitization induces T helper 2-type dermatitis and strong prohevein-specific IgE response. J Invest Dermatol 2003;120:633-640.
Gonipeta B, Parvataneni S, Tempelman RJ, Gangur V: An adjuvant-free mouse model to evaluate the allergenicity of milk whey protein. J Dairy Sci 2009;92:4738-4744.
Birmingham NP, Parvataneni S, Hassan HM, Harkema J, Samineni S, Navuluri L, Kelly CJ, Gangur V: An adjuvant-free mouse model of tree nut allergy using hazelnut as a model tree nut. Int Arch Allergy Immunol 2007;144:203-210.
Koppelman SJ, Vlooswijk RA, Knippels LM, Hessing M, Knol EF, van Reijsen FC, Bruijnzeel-Koomen CA: Quantification of major peanut allergens Ara h 1 and Ara h 2 in the peanut varieties Runner, Spanish, Virginia, and Valencia, bred in different parts of the world. Allergy 2001;56:132-137.
Johnson RM, Barnes CS: Airborne concentrations of peanut protein. Allergy Asthma Proc 2013;34:59-64.
Brough HA, Santos AF, Makinson K, Penagos M, Stephens AC, Douiri A, Fox AT, Du Toit G, Turcanu V, Lack G: Peanut protein in household dust is related to household peanut consumption and is biologically active. J Allergy Clin Immunol 2013;132:630-638.
Watson WT, Woodrow A, Stadnyk AW: Persistence of peanut allergen on a table surface. Allergy Asthma Clin Immunol 2013;9:7.
Perry TT, Conover-Walker MK, Pomés A, Chapman MD, Wood RA: Distribution of peanut allergen in the environment. J Allergy Clin Immunol 2004;113:973-976.
Leyva-Castillo JM, Hener P, Jiang H, Li M: TSLP produced by keratinocytes promotes allergen sensitization through skin and thereby triggers atopic march in mice. J Invest Dermatol 2013;133:154-163.
Jiang H, Hener P, Li J, Li M: Skin thymic stromal lymphopoietin promotes airway sensitization to inhalant house dust mites leading to allergic asthma in mice. Allergy 2012;67:1078-1082.
Willart MA, Deswarte K, Pouliot P, Braun H, Beyaert R, Lambrecht BN, Hammad H: Interleukin-1α controls allergic sensitization to inhaled house dust mite via the epithelial release of GM-CSF and IL-33. J Exp Med 2012;209:1505-1517.
Fujita J, Kawaguchi M, Kokubu F, Ohara G, Ota K, Huang SK, Morishima Y, Ishii Y, Satoh H, Sakamoto T, Hizawa N: Interleukin-33 induces interleukin-17f in bronchial epithelial cells. Allergy 2012;67:744-750.
Adel-Patient K, Ah-Leung S, Bernard H, Durieux-Alexandrenne C, Créminon C, Wal JM: Oral sensitization to peanut is highly enhanced by application of peanut extracts to intact skin, but is prevented when CPG and cholera toxin are added. Int Arch Allergy Immunol 2007;143:10-20.
Heederik D, Henneberger PK, Redlich CA; Asthma ETFotMoW-r: Primary prevention: exposure reduction, skin exposure and respiratory protection. Eur Respir Rev 2012;21:112-124.
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