INTRODUCTION
Allergic diseases such as asthma, atopic dermatitis (AD), allergic rhinitis (AR) and food allergy affect ~20% of the population worldwide (1). The most prominent cells involved in allergy are the mast cells (MCs), considered the primum movens of the reaction upon their activation by IgE-allergen, followed by the eosinophils (Eos), that heavily contribute to the inflammatory outcome. Moreover, their soluble and physical crosstalk that we identified and named the Allergic Effector Unit (AEU), is a key factor increasing the pro-inflammatory potential of the two cells and hence the allergic inflammation (AI) (2, 3). In addition, several reports have shown the nearly exclusive presence of S. aureus (SA) and its exotoxins, such as SA enterotoxin B (SEB) and others in asthma, AR, food allergy and AD (4–6). Interestingly, SA was found to directly bind and activate MCs (7) and Eos (8).
Until recently, the most common protocol used in the investigation of AI in mice involved the use of the antigen ovalbumin (OVA), together with aluminum hydroxide (Alum). However, it was shown that Alum can activate the innate immune response by activating the NLRP3 inflammasome through increasing uric acid levels (9). Furthermore, Alum was found to induce AI via activation of dendritic cells (DCs) independently of MCs (10). Indeed, it was shown that 24h following intraperitoneal (i.p) injection, DCs and neutrophils were detected and increased during the inflammation in the peritoneal cavity, while MCs and macrophages, typical resident cells, decreased (10). In addition, Alum co-administration with an antigen was demonstrated not to be necessary for the induction of acute allergic airway inflammation (11) and of AD (12).
Noteworthy, BALB/C mice are often used in AI studies since they are prone to Th2 responses. Nevertheless, C57BL6 are employed more often because of the availability of transgenic and knockout (KO) strains based on their background (13, 14).
Therefore, our aim was to develop a mast cell-dependent, rapid and reproducible model of AI with the closest features to human Th2 allergic diseases in C57BL6 mice. Hence, we established an allergic peritonitis (AP) model by employing sensitization and challenge with OVA and SEB.