Journal Article
. 2019 Mar; 7(1):41-51.
doi: 10.1002/iid3.242.

Mouse strain differences in response to oral immunotherapy for peanut allergy

Laura Wagenaar 1 Marianne W H C Bol-Schoenmakers 1 Giulio Giustarini 1 Johan Garssen 2 Joost J Smit 1 Raymond H H Pieters 1 
Affiliations
  • PMID: 30838819
  •     32 References
  •     3 citations

Abstract

Background: Promising therapies for food allergy are emerging, mostly based on animal experimentation. However, different mouse strains are used, which may make it hard to compare experiments. The current study investigated whether the immunological differences between C3H/HeOuJ (C3H) and BALB/c mice lead to differences in efficacy of peanut-specific immunotherapy.

Methods: After sensitization using peanut extract (PE), C3H and BALB/c mice received oral immunotherapy (OIT) by intragastric dosing for three weeks. Hereafter, mice were exposed to PE via the intradermal, intragastric and intraperitoneal route, to determine allergic outcomes. Furthermore, PE-specific antibody and cytokine production were determined and the number of various immune cells at different time points during the study were measured.

Results: OIT protected C3H mice against anaphylaxis, whereas no anaphylaxis was seen in BALB/c mice. In contrast, OIT induced an increase in MMCP-1 levels in BALB/c mice but not in C3H mice. No effect of OIT on the acute allergic skin response was observed in either strain. Specific antibody responses showed similar patterns in both strains for IgA and IgG1. IgE levels were a tenfold higher in BALB/c mice and after the intragastric challenge (day 70) OIT-treated BALB/c mice showed induced IgE levels. Moreover, in C3H mice IgG2a levels were higher and increased in response to OIT and challenges. After the final challenge, but not at other timepoints MLN-derived lymphocytes from OIT-treated BALB/c mice produced less IL-13 and IL-5 compared to control-treated mice, whereas no differences were seen in case of C3H mice.

Conclusions: Taken together, these results show that the C3H strain is more suitable to study clinical outcomes of OIT, whereas the BALB/c strain is more optimal to study T cell responses.

Keywords: BALB/c; C3H/HeOuJ; immunotherapy; mouse model; peanut allergy.

A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response.
Pooja Varshney, Stacie M Jones, +11 authors, A Wesley Burks.
J Allergy Clin Immunol, 2011 Mar 08; 127(3). PMID: 21377034    Free PMC article.
Highly Cited.
Differences in the Anaphylactic Response between C3H/HeOuJ and BALB/c Mice.
Guadalupe Marco-Martín, Alejandro La Rotta Hernández, +3 authors, María Luisa Baeza.
Int Arch Allergy Immunol, 2017 Aug 30; 173(4). PMID: 28850948
Measurement of IgE antibodies against purified grass pollen allergens (Lol p 1, 2, 3 and 5) during immunotherapy.
R Van Ree, W A Van Leeuwen, +10 authors, R C Aalberse.
Clin Exp Allergy, 1997 Jan 01; 27(1). PMID: 9117883
Update on food allergy.
A Carrard, D Rizzuti, C Sokollik.
Allergy, 2015 Oct 08; 70(12). PMID: 26443043
Review.
An Examination of Clinical and Immunologic Outcomes in Food Allergen Immunotherapy by Route of Administration.
David Chiang, M Cecilia Berin.
Curr Allergy Asthma Rep, 2015 Jul 05; 15(6). PMID: 26141581
Review.
Peanut allergy.
A Wesley Burks.
Lancet, 2008 May 06; 371(9623). PMID: 18456104
Review.
Antibody Production, Anaphylactic Signs, and T-Cell Responses Induced by Oral Sensitization With Ovalbumin in BALB/c and C3H/HeOuJ Mice.
Alba Pablos-Tanarro, Ivan López-Expósito, +2 authors, Elena Molina.
Allergy Asthma Immunol Res, 2016 Mar 01; 8(3). PMID: 26922934    Free PMC article.
Orally-Induced Intestinal CD4+ CD25+ FoxP3+ Treg Controlled Undesired Responses towards Oral Antigens and Effectively Dampened Food Allergic Reactions.
Paola Lorena Smaldini, María Lucía Orsini Delgado, Carlos Alberto Fossati, Guillermo Horacio Docena.
PLoS One, 2015 Oct 31; 10(10). PMID: 26517875    Free PMC article.
CD200R surface expression as a marker of murine basophil activation.
M N Torrero, D Larson, M P Hübner, E Mitre.
Clin Exp Allergy, 2009 Jan 13; 39(3). PMID: 19134017    Free PMC article.
Allergen immunotherapy: 100 years, but it does not look like.
F Frati, C Incorvaia, C Lombardi, G Senna.
Eur Ann Allergy Clin Immunol, 2012 Aug 22; 44(3). PMID: 22905590
Review.
Differences in phenotype, homing properties and suppressive activities of regulatory T cells induced by epicutaneous, oral or sublingual immunotherapy in mice sensitized to peanut.
Vincent Dioszeghy, Lucie Mondoulet, +5 authors, Pierre-Henri Benhamou.
Cell Mol Immunol, 2016 Apr 12; 14(9). PMID: 27063469    Free PMC article.
CTLA-4 signaling regulates the intensity of hypersensitivity responses to food antigens, but is not decisive in the induction of sensitization.
Femke van Wijk, Sanne Hoeks, +5 authors, Raymond Pieters.
J Immunol, 2004 Dec 22; 174(1). PMID: 15611239
Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract.
H S Nelson, J Lahr, +2 authors, D Leung.
J Allergy Clin Immunol, 1997 Jun 01; 99(6 Pt 1). PMID: 9215240
Highly Cited.
Oral immunotherapy induces IgG antibodies that act through FcγRIIb to suppress IgE-mediated hypersensitivity.
Oliver T Burton, Stephanie L Logsdon, +9 authors, Hans C Oettgen.
J Allergy Clin Immunol, 2014 Jul 22; 134(6). PMID: 25042981    Free PMC article.
Highly Cited.
Food allergy: is prevalence increasing?
Mimi L K Tang, Raymond J Mullins.
Intern Med J, 2017 Mar 06; 47(3). PMID: 28260260
Mixed antibody and T cell responses to peanut and the peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 in an oral sensitization model.
F van Wijk, S Hartgring, +2 authors, L M J Knippels.
Clin Exp Allergy, 2004 Sep 07; 34(9). PMID: 15347376
Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction.
U Staden, C Rolinck-Werninghaus, +3 authors, K Beyer.
Allergy, 2007 Oct 09; 62(11). PMID: 17919140
Treatment of peanut allergy with rush immunotherapy.
J J Oppenheimer, H S Nelson, +2 authors, D Y Leung.
J Allergy Clin Immunol, 1992 Aug 01; 90(2). PMID: 1500630
Highly Cited.
Oral tolerance induction does not resolve gastrointestinal inflammation in a mouse model of food allergy.
Manja Burggraf, Haruyo Nakajima-Adachi, +5 authors, Masako Toda.
Mol Nutr Food Res, 2011 Jun 30; 55(10). PMID: 21714123
A practical view of immunotherapy for food allergy.
Tae Won Song.
Korean J Pediatr, 2016 Mar 10; 59(2). PMID: 26958062    Free PMC article.
Review.
Genetic susceptibility to food allergy is linked to differential TH2-TH1 responses in C3H/HeJ and BALB/c mice.
Vivian Morafo, Kamal Srivastava, +4 authors, AndXiu-Min Li.
J Allergy Clin Immunol, 2003 May 14; 111(5). PMID: 12743580
Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy.
L Mondoulet, V Dioszeghy, +3 authors, P-H Benhamou.
Clin Exp Allergy, 2009 Dec 17; 40(4). PMID: 20002446
Oral immunotherapy induces local protective mechanisms in the gastrointestinal mucosa.
Stephanie A Leonard, Gustavo Martos, +2 authors, M Cecilia Berin.
J Allergy Clin Immunol, 2012 May 05; 129(6). PMID: 22554705    Free PMC article.
Grass tablet sublingual immunotherapy downregulates the TH2 cytokine response followed by regulatory T-cell generation.
Abel Suárez-Fueyo, Tania Ramos, +8 authors, Rosa Varona.
J Allergy Clin Immunol, 2013 Dec 03; 133(1). PMID: 24290282
Contribution of classic and alternative effector pathways in peanut-induced anaphylactic responses.
Joost J Smit, Karina Willemsen, +7 authors, Raymond H H Pieters.
PLoS One, 2011 Dec 24; 6(12). PMID: 22194949    Free PMC article.
Food allergy.
Julie Wang, Hugh A Sampson.
J Clin Invest, 2011 Mar 03; 121(3). PMID: 21364287    Free PMC article.
Review.
Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.
U Nurmatov, S Dhami, +24 authors, A Sheikh.
Allergy, 2017 Jan 07; 72(8). PMID: 28058751
Highly Cited. Systematic Review.
Genetic influence on immune phenotype revealed strain-specific variations in peripheral blood lineages.
Stefka B Petkova, Rong Yuan, +3 authors, Beverly Paigen.
Physiol Genomics, 2008 Jun 12; 34(3). PMID: 18544662    Free PMC article.
Mouse strain differences in response to oral immunotherapy for peanut allergy.
Laura Wagenaar, Marianne W H C Bol-Schoenmakers, +3 authors, Raymond H H Pieters.
Immun Inflamm Dis, 2019 Mar 07; 7(1). PMID: 30838819    Free PMC article.
The efficacy of oral and subcutaneous antigen-specific immunotherapy in murine cow's milk- and peanut allergy models.
Marlotte M Vonk, Laura Wagenaar, +5 authors, Johan Garssen.
Clin Transl Allergy, 2017 Oct 13; 7. PMID: 29021893    Free PMC article.
Spleen B cells from BALB/c are more prone to activation than spleen B cells from C57BL/6 mice during a secondary immune response to cruzipain.
Andrea Pellegrini, Natalia Guiñazú, +5 authors, Susana Gea.
Int Immunol, 2007 Oct 30; 19(12). PMID: 17965451
Prebiotics, probiotics, synbiotics, and the immune system: experimental data and clinical evidence.
Remo Frei, Mübeccel Akdis, Liam O'Mahony.
Curr Opin Gastroenterol, 2015 Jan 17; 31(2). PMID: 25594887
Review.
Mouse strain differences in response to oral immunotherapy for peanut allergy.
Laura Wagenaar, Marianne W H C Bol-Schoenmakers, +3 authors, Raymond H H Pieters.
Immun Inflamm Dis, 2019 Mar 07; 7(1). PMID: 30838819    Free PMC article.
A Comprehensive Review on Natural Bioactive Compounds and Probiotics as Potential Therapeutics in Food Allergy Treatment.
Kunal Pratap, Aya C Taki, +2 authors, Sandip D Kamath.
Front Immunol, 2020 Jul 17; 11. PMID: 32670266    Free PMC article.
Review.
Oral Immunotherapy Using Probiotic Ice Cream Containing Recombinant Food-Grade Lactococcus lactis Which Inhibited Allergic Responses in a BALB/c Mouse Model.
Alireza Vasiee, Fereshteh Falah, +2 authors, Seyed Ali Mortazavi.
J Immunol Res, 2020 Oct 09; 2020. PMID: 33029537    Free PMC article.