A single priming event prevents oral tolerance to peanut

被引:4
作者
Smeekens, Johanna M. [1 ,2 ,3 ]
Immormino, Robert M. [1 ]
Kesselring, Janelle R. [1 ,2 ]
Turner, Andrew V. [1 ,2 ]
Kulis, Michael D. [1 ,2 ]
Moran, Timothy P. [1 ]
机构
[1] UNC Sch Med, Dept Pediat, Chapel Hill, NC USA
[2] UNC Sch Med, Dept Pediat, UNC Food Allergy Initiat, Chapel Hill, NC USA
[3] UNC Sch Med, Dept Pediat, 116 Manning Dr,Mary Ellen Jones Bldg Room 3310, Chapel Hill, NC 27599 USA
基金
美国国家卫生研究院;
关键词
airway sensitization; CD154 T cells; food allergy; LPS; mouse model; oral tolerance; peanut allergy; T-CELLS; HIGH-RISK; EXPOSURE; ALLERGY; SENSITIZATION; PROTEIN; INFANTS; ANTIGEN; CONSUMPTION; ACTIVATION;
D O I
10.1111/cea.14373
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Indoor dust (ID) is a source of peanut proteins and immunostimulatory adjuvants (e.g. LPS) that can promote airway sensitization to peanut. We aimed to determine whether a single airway exposure to peanut plus adjuvant is sufficient to prevent oral tolerance. Methods: To determine the effect of a single priming event, C57BL/6J mice were exposed once to peanut plus adjuvant through the airway, followed by either airway or low-dose oral exposure to peanut, and assessed for peanut allergy. Oral tolerance was investigated by feeding high-dose peanut followed by airway sensitization. To determine whether a single priming could prevent oral tolerance, the high-dose peanut regimen was applied after a single airway exposure to peanut plus adjuvant. Peanut-specific IgE and IgG1 were quantified, and mice were challenged to peanut to assess allergy. Peanut-specific CD4(+) memory T cells (CD4(+)TCR beta(+)CD44(hi)CD154(+)) were quantified in mediastinal lymph nodes following airway priming. Results: Mice co-exposed to peanut with LPS or ID through the airway were primed to develop peanut allergy after subsequent low-dose oral or airway exposures to peanut. Oral tolerance was induced in mice fed high-dose peanut prior to airway sensitization. In contrast, mice fed high-dose peanut following a single airway exposure to peanut plus adjuvant led to allergy. Peanut-specific CD4(+) memory T cells were detected as early as 7 days after the single airway priming with peanut plus adjuvant, however, delaying peanut feeding even 1 day following priming led to allergy, whereas peanut feeding the same day as priming led to tolerance. Conclusions: A single airway exposure to peanut plus adjuvant is sufficient to prime the immune system to develop allergy following subsequent high-dose oral exposure. These results highlight the importance of introducing peanut as early as possible to prevent sensitization through a non-oral priming event.
引用
收藏
页码:930 / 940
页数:11
相关论文
共 49 条
[1]  
Baker SS, 2000, PEDIATRICS, V106, P346
[2]   Antigenic Liposomes for Generation of Disease-specific Antibodies [J].
Bednar, Kyle J. ;
Hardy, Lakeya ;
Smeekens, Johanna ;
Raghuwanshi, Dharmendra ;
Duan, Shiteng ;
Kulis, Mike D. ;
Macauley, Matthew S. .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2018, (140)
[3]   Circulating allergen-specific TH2 lymphocytes: CCR4+ rather than CLA+ is the predominant phenotype in peanut-allergic subjects [J].
Blom, Lars H. ;
Juel-Berg, Nanna ;
Larsen, Lau Fabricius ;
Hansen, Kirsten S. ;
Poulsen, Lars K. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2018, 141 (04) :1498-+
[4]   Route of Sensitization to Peanut Influences Immune Cell Recruitment at Various Mucosal Sites in Mouse: An Integrative Analysis [J].
Briard, Melanie ;
Guinot, Marine ;
Grauso, Marta ;
Guillon, Blanche ;
Hazebrouck, Stephane ;
Bernard, Herve ;
Bouchaud, Gregory ;
Michel, Marie-Laure ;
Adel-Patient, Karine .
NUTRIENTS, 2022, 14 (04)
[5]   Environmental peanut exposure increases the risk of peanut sensitization in high-risk children [J].
Brough, H. A. ;
Kull, I. ;
Richards, K. ;
Hallner, E. ;
Soderhall, C. ;
Douiri, A. ;
Penagos, M. ;
Melen, E. ;
Bergstrom, A. ;
Turcanu, V. ;
Wickman, M. ;
Lack, G. .
CLINICAL AND EXPERIMENTAL ALLERGY, 2018, 48 (05) :586-593
[6]   Early intervention and prevention of allergic diseases [J].
Brough, Helen A. ;
Lanser, Bruce Joshua ;
Sindher, Sayantani B. ;
Teng, Joyce M. C. ;
Leung, Donald Y. M. ;
Venter, Carina ;
Chan, Susan M. ;
Santos, Alexandra F. ;
Bahnson, Henry T. ;
Guttman-Yassky, Emma ;
Gupta, Ruchi S. ;
Lack, Gideon ;
Ciaccio, Christina E. ;
Sampath, Vanitha ;
Nadeau, Kari C. ;
Nagler, Cathryn R. .
ALLERGY, 2022, 77 (02) :416-441
[7]   Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented? [J].
Brough, Helen A. ;
Nadeau, Kari C. ;
Sindher, Sayantani B. ;
Alkotob, Shifaa S. ;
Chan, Susan ;
Bahnson, Henry ;
Leung, Donald Y. M. ;
Lack, Gideon .
ALLERGY, 2020, 75 (09) :2185-2205
[8]   Mass spectrometry confirmation that clinically important peanut protein allergens are present in household dust [J].
Brough, Helen A. ;
Mills, Elizabeth Naomi Clare ;
Richards, Kerry ;
Lack, Gideon ;
Johnson, Philip E. .
ALLERGY, 2020, 75 (03) :709-712
[9]   Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy [J].
Brough, Helen A. ;
Liu, Andrew H. ;
Sicherer, Scott ;
Makinson, Kerry ;
Douiri, Abdel ;
Brown, Sara J. ;
Stephens, Alick C. ;
McLean, W. H. Irwin ;
Turcanu, Victor ;
Wood, Robert A. ;
Jones, Stacie M. ;
Burks, Wesley ;
Dawson, Peter ;
Stablein, Donald ;
Sampson, Hugh ;
Lack, Gideon .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2015, 135 (01) :164-U249
[10]   Peanut allergy: Effect of environmental peanut exposure in children with filaggrin loss-of-function mutations [J].
Brough, Helen A. ;
Simpson, Angela ;
Makinson, Kerry ;
Hankinson, Jenny ;
Brown, Sara ;
Douiri, Abdel ;
Belgrave, Danielle C. M. ;
Penagos, Martin ;
Stephens, Alick C. ;
McLean, W. H. Irwin ;
Turcanu, Victor ;
Nicolaou, Nicolaos ;
Custovic, Adnan ;
Lack, Gideon .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2014, 134 (04) :867-U472