The cell surface receptor Slamf6 modulates innate immune responses during Citrobacter rodentium-induced colitis

The homophilic cell surface receptors CD150 (Slamf1) and CD352 (Slamf6) are known to modulate adaptive immune responses. Although the Th17 response was enhanced in Slamf6 –/– C57BL/6 mice upon oral infection with Citrobacter rodentium, the pathologic consequences are indistinguishable from an infection of wild-type C57BL/6 mice. Using a reporter-based binding assay, we show that Slamf6 can engage structures on the outer cell membrane of several Gram– bacteria. Therefore, we examined whether Slamf6, like Slamf1, is also involved in innate responses to bacteria and regulates peripheral inflammation by assessing the outcome of C. rodentium infections in Rag –/– mice. Surprisingly, the pathology and immune responses in the lamina propria of C. rodentium-infected Slamf6 –/– Rag –/– mice were markedly reduced as compared with those of Rag –/– mice. Infiltration of inflammatory phagocytes into the lamina propria was consistently lower in Slamf6 –/– Rag –/– mice than in Rag –/– animals. Concomitant with the reduced systemic translocation of the bacteria was an enhanced production of IL-22, suggesting that Slamf6 suppresses a mucosal protective program. Furthermore, administering a mAb (330) that inhibits bacterial interactions with Slamf6 to Rag –/– mice ameliorated the infection compared with a control antibody. We conclude th...
Source: International Immunology - Category: Allergy & Immunology Authors: Tags: Original Research Source Type: research