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
Affiliations
Khaled Zubeidat
Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem 9112102, Israel
Yasmin Jaber
Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem 9112102, Israel
Yasmin Saba
Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem 9112102, Israel
Or Barel
Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem 9112102, Israel
Reem Naamneh
Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem 9112102, Israel
Yasmin Netanely
Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem 9112102, Israel
Yael Horev
Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem 9112102, Israel
Luba Eli-berchoer
Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem 9112102, Israel
Amjad Shhadeh
Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem 9112102, Israel
Omri Yosef
The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, Hebrew University, Jerusalem 9112102, Israel
Eliran Arbib
The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, Hebrew University, Jerusalem 9112102, Israel
Gili Betser-Cohen
Division of Identification and Forensic Science, Police National HQ, Jerusalem, Israel
Chen Nadler
Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel; Department of Oral Medicine, Sedation & Maxillofacial Imaging, Hadassah Medical Center, Jerusalem 9112102, Israel
Hagit Shapiro
System Immunology Department, Weizmann Institute of Science, Rehovot 7632706, Israel
Eran Elinav
System Immunology Department, Weizmann Institute of Science, Rehovot 7632706, Israel; Microbe & Cancer Division, DKFZ, Heidelberg, Germany
Doron J. Aframian
Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel; Department of Oral Medicine, Sedation & Maxillofacial Imaging, Hadassah Medical Center, Jerusalem 9112102, Israel
Asaf Wilensky
Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel; Department of Periodontology, Hadassah Medical Center, Jerusalem 9112102, Israel
Avi-Hai Hovav
Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem 9112102, Israel; Corresponding author
Summary: 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.
