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

doi:10.1016/j.celrep.2022.111981

Microbiota-dependent and -independent postnatal development of salivary immunity

Cell Rep. 2023 Jan 31;42(1):111981. doi: 10.1016/j.celrep.2022.111981. Epub 2023 Jan 7.

Authors

Khaled Zubeidat¹, Yasmin Jaber¹, Yasmin Saba¹, Or Barel¹, Reem Naamneh¹, Yasmin Netanely¹, Yael Horev¹, Luba Eli-Berchoer¹, Amjad Shhadeh¹, Omri Yosef², Eliran Arbib², Gili Betser-Cohen³, Chen Nadler⁴, Hagit Shapiro⁵, Eran Elinav⁶, Doron J Aframian⁴, Asaf Wilensky⁷, Avi-Hai Hovav⁸

Affiliations

¹ Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem 9112102, Israel.
² The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, Hebrew University, Jerusalem 9112102, Israel.
³ Division of Identification and Forensic Science, Police National HQ, Jerusalem, Israel.
⁴ Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel; Department of Oral Medicine, Sedation & Maxillofacial Imaging, Hadassah Medical Center, Jerusalem 9112102, Israel.
⁵ System Immunology Department, Weizmann Institute of Science, Rehovot 7632706, Israel.
⁶ System Immunology Department, Weizmann Institute of Science, Rehovot 7632706, Israel; Microbe & Cancer Division, DKFZ, Heidelberg, Germany.
⁷ Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel; Department of Periodontology, Hadassah Medical Center, Jerusalem 9112102, Israel.
⁸ Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem 9112102, Israel. Electronic address: avihaih@ekmd.huji.ac.il.

PMID: 36640306
DOI: 10.1016/j.celrep.2022.111981

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.

Keywords: CP: Immunology; CP: Microbiology; IgA; IgG; oral mucosa; postnatal; salivary glands; weaning.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Immunoglobulin G
Mice
Microbiota*
Receptors, Polymeric Immunoglobulin*
Saliva
Salivary Glands

Substances

Receptors, Polymeric Immunoglobulin
Immunoglobulin G