Microbiota-dependent and -independent postnatal development of salivary immunity
Khaled Zubeidat, Yasmin Jaber, Yasmin Saba, Or Barel, Reem Naamneh, Yasmin Netanely, Yael Horev, Luba Eli‐Berchoer, Amjad Shhadeh, Omri Yosef, Eliran Arbib, Gili Betser-Cohen, Chen Nadler, Hagit Shapiro, Eran Elinav, Doron J. Aframian, Asaf Wilensky, Avi‐Hai Hovav
Abstract
While saliva regulates the interplay between the microbiota and the oral immune system, the mechanisms establishing postnatal salivary immunity are ill-defined. Here, we show that high levels of neutrophils and neonatal Fc receptor (FcRn)-transferred maternal IgG are temporarily present in the neonatal murine salivary glands in a microbiota-independent manner. During weaning, neutrophils, FcRn, and IgG decrease in the salivary glands, while the polymeric immunoglobulin receptor (pIgR) is upregulated in a growth arrest-specific 6 (GAS6)-dependent manner independent of the microbiota. Production of salivary IgA begins following weaning and relies on CD4-help, IL-17, and the microbiota. The weaning phase is characterized by a transient accumulation of dendritic cells capable of migrating from the oral mucosa to the salivary glands upon exposure to microbial challenges and activating T cells. This study reveals the postnatal mechanisms developed in the salivary glands to induce immunity and proposes the salivary glands as an immune inductive site.