ORIGINAL ARTICLE EXPERIMENTAL ALLERGY AND IMMUNOLOGY Neonatal colonization of mice with Lactobacillus plantarum producing the aeroallergen Bet v 1 biases towards Th1 and T-regulatory responses upon systemic sensitization M. Schwarzer 1* , A. Repa 2,3* , C. Daniel 4 , I. Schabussova 2 , T. Hrncir 1 , B. Pot 4 , R. Stepankova 1 , T. Hudcovic 1 , A. Pollak 3 , H. Tlaskalova-Hogenova 1 , U. Wiedermann 2 & H. Kozakova 1 1 Department of Immunology and Gnotobiology, Institute of Microbiology of the Academy of Sciences of the Czech Republic, v. v. i., Novy Hradek, Czech Republic; 2 Department of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna; 3 Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria; 4 Institut Pasteur de Lille, Lactic acid Bacteria & Mucosal Immunity, Center for Infection and Immunity of Lille, Univ Lille Nord de France, CNRS, UMR 8204, Institut National de la Sante ´ et de la Recherche Me ´ dicale, U1019, Lille, France To cite this article: Schwarzer M, Repa A, Daniel C, Schabussova I, Hrncir T, Pot B, Stepankova R, Hudcovic T, Pollak A, Tlaskalova-Hogenova H, Wiedermann U, Kozakova H. Neonatal colonization of mice with Lactobacillus plantarum producing the aeroallergen Bet v 1 biases towards Th1 and T-regulatory responses upon systemic sensitization. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02488.x. Allergic diseases have become a substantial public health burden in industrialized countries, and their prevalence has steadily increased over the last decades. At present, allergen- specific immunotherapy (SIT) is the only curative and dis- ease-modifying treatment in the majority of patients (1), which however has some drawbacks: SIT vaccines contain crude extracts from natural sources containing a mixture of allergens and contaminant components, which may pose a risk for de novo sensitization to new allergens (2). In this respect, standardized recombinant allergens could improve the safety profile and efficacy of SIT (3). To keep the aller- gens at the injection site, traditional SIT utilizes aluminium hydroxide as an adjuvant. Although aluminium adjuvants are widely used with good results in humans, they promote Th2-like responses (4), which might reduce SIT efficacy. Recently, lactic acid bacteria (LAB) have been introduced Keywords allergy; germ-free mice; mucosal immunity; primary prevention; recombinant lactic acid bacteria. Correspondence Univ. Prof. Dr. Ursula Wiedermann, Department of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University of Vienna, Kinderspitalgasse 15, 1090 Vienna, Austria. Tel.: +431-4049-064890 Fax: +431-4049-064899 E-mail: ursula.wiedermann@meduniwien.ac.at *Both authors contributed equally to the work. Accepted for publication 18 August 2010 DOI:10.1111/j.1398-9995.2010.02488.x Edited by: Hans-Uwe Simon Abstract Background: The use of recombinant lactic acid bacteria (LAB) as vehicles for mucosal delivery of recombinant allergens is an attractive concept for antigen- defined allergy prevention/treatment. Interventions with LAB are of increasing inter- est early in life when immune programming is initiated. Here, we investigated the effect of neonatal colonization with a recombinant LAB producing the major birch pollen allergen Bet v 1 in a murine model of type I allergy. Methods: We constructed a recombinant Lactobacillus (L.) plantarum NCIMB8826 strain constitutively producing Bet v 1 to be used for natural mother-to-offspring mono-colonization of germ-free BALB/c mice. Allergen-specific immunomodulatory effects of the colonization on humoral and cellular immune responses were investi- gated prior and after sensitization to Bet v 1. Results: Mono-colonization with the Bet v 1 producing L. plantarum induced a Th1-biased immune response at the cellular level, evident in IFN-c production of splenocytes upon stimulation with Bet v 1. After sensitization with Bet v 1 these mice displayed suppressed IL-4 and IL-5 production in spleen and mesenteric lymph node cell cultures as well as decreased allergen-specific antibody responses (IgG1, IgG2a, and IgE) in sera. This suppression was associated with a significant up-regu- lation of the regulatory marker Foxp3 at the mRNA level in the spleen cells. Conclusion: Intervention at birth with a live recombinant L. plantarum producing a clinically relevant allergen reduces experimental allergy and might therefore become an effective strategy for early intervention against the onset of allergic diseases. Allergy ª 2010 John Wiley & Sons A/S