Hornikova Tereza, Jelinkova Anna, Jiraskova Zakostelska Zuzana, Thon Tomas, Coufal Stepan, Polouckova Andrea, Kopelentova Eliska, Kverka Miloslav, Makovicky Peter, Tlaskalova-Hogenova Helena, Sediva Anna, Schwarzer Martin, Srutkova Dagmar
Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, Novy Hradek, Czechia.
Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia.
Front Immunol. 2025 Jan 29;15:1509691. doi: 10.3389/fimmu.2024.1509691. eCollection 2024.
The dual allergen exposure hypothesis states that sensitization to food antigens occurs through a damaged skin barrier in individuals with no previous oral tolerance to certain foods. However, the resulting allergic reaction could depend on factors such as the host's genetic predisposition as well as the skin and gut microbiota.
Specific-pathogen-free BALB/c and C57BL/6 and germ-free (GF) BALB/c mice were epicutaneously sensitized with ovalbumin (OVA) via dorsal tape-stripped skin and challenged with OVA by intragastric gavage. The development of food allergy (FA) symptoms, the Th2 and mast cell immune response and differences in the skin and gut microbiota were investigated.
BALB/c mice, but not C57BL/6 mice, showed severe clinical signs of FA (hypothermia, diarrhea) as well as a stronger serum antibody response and Th2 cytokine secretion in the spleen and jejunum after OVA-treatment. The increased mast cell count correlated with higher MCPT-1 production and histidine decarboxylase mRNA expression in the jejunum of these mice. The 16S rRNA sequencing analysis revealed lower abundance of short-chain fatty acids producing bacteria in the gut microbiome of OVA-treated BALB/c mice. Changes in the β-diversity of the gut microbiome reflect both the genetic background as well as the OVA treatment of experimental mice. Compared to SPF mice, GF mice developed more severe anaphylactic hypothermia but no diarrhea, although they had a higher mast cell count, increased MCPT-1 production in the jejunum and serum, and increased arachidonate 5-lipoxygenase mRNA expression.
We show that the BALB/c mice are a mouse strain of choice for model of adjuvant-free epicutaneous sensitization through the disrupted skin barrier and following food allergy development. Our results highlight the significant influence of genetic background and microbiota on food allergy susceptibility, emphasizing the complex interplay between these factors in the allergic response.
双重过敏原暴露假说认为，对于某些食物此前没有口服耐受性的个体，其对食物抗原的致敏是通过受损的皮肤屏障发生的。然而，由此产生的过敏反应可能取决于宿主的遗传易感性以及皮肤和肠道微生物群等因素。
将无特定病原体的BALB/c和C57BL/6小鼠以及无菌（GF）BALB/c小鼠通过背部胶带剥离皮肤经皮用卵清蛋白（OVA）致敏，然后通过灌胃用OVA进行激发。研究食物过敏（FA）症状的发展、Th2和肥大细胞免疫反应以及皮肤和肠道微生物群的差异。
OVA处理后，BALB/c小鼠而非C57BL/6小鼠出现了严重的FA临床症状（体温过低、腹泻），并且在脾脏和空肠中表现出更强的血清抗体反应和Th2细胞因子分泌。这些小鼠空肠中肥大细胞计数的增加与更高的MCPT-1产生以及组氨酸脱羧酶mRNA表达相关。16S rRNA测序分析显示，OVA处理的BALB/c小鼠肠道微生物群中产生短链脂肪酸的细菌丰度较低。肠道微生物群β多样性的变化反映了实验小鼠的遗传背景以及OVA处理情况。与无特定病原体小鼠相比，GF小鼠出现了更严重的过敏性体温过低但没有腹泻，尽管它们的肥大细胞计数更高、空肠和血清中MCPT-1产生增加以及花生四烯酸5-脂氧合酶mRNA表达增加。
我们表明，BALB/c小鼠是通过破坏的皮肤屏障进行无佐剂经皮致敏以及后续食物过敏发展模型的首选小鼠品系。我们的结果突出了遗传背景和微生物群对食物过敏易感性的重大影响，强调了这些因素在过敏反应中的复杂相互作用。
