2B4, CD48 and Staphylococcus aureus enterotoxin B: a party for three in allergic inflammation.
2The Concern Foundation Laboratories at the Lautenberg Centre for Immunology and Cancer Research, Imric, Faculty of Medicine, Hebrew University Hadassah Medical Center, Israel
3Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Israel
Mast cells (MCs) and eosinophils (Eos), the main players of allergy characterized by Staphylococcus aureus (SA) colonization, physically crosstalk via a CD48-2B4 interactions (Allergic Effector Unit). We have found that SA and its exotoxins activate MCs and Eos via CD48, a GPI receptor belonging to the CD2 family.
We have here hypothesized that CD48 ligand 2B4 might also bind SA exotoxins, thereby further participating in AEU.
We therefore aimed to elucidate Staphylococcal Enterotoxin B (SEB) interactions with 2B4 and CD48: 1) in vitro using 2B4 and CD48-Fc and BW cells expressing 2B4 or by incubating 2B4KO bone marrow derived MCs and Eos (BMMCs and BMEos) with SEB :2) in silico:3) in vivo by inducing SEB peritonitis in 2B4KO mice.
We showed that SEB binds 2B4 but does not activate 2B4. Interestingly SEB increased the activation of BW-2B4 cells preincubated with CD48-Fc. 2B4KO BMMCs and BMEos showed decreased activation by SEB (TNF-a, and EPO/sCD48 respectively). In silico analysis suggested distinct binding sites of CD48 and SEB on 2B4. Dimerization of 2B4 seems to increase SEB binding affinity. SEB peritonitis resulted in reduction of inflammatory features but not of Eos percentages in 2B4-KO mice compared to WT mice.
Our results demonstrate that SA colonization (represented by SEB) affects MCs and Eos in the AEU through an interaction with both CD48 and 2B4. This may elucidate the strong pro-inflammatory impact that SA has in allergic and non-allergic inflammation.
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