MyD88 Deficiency Alters Expression of Antimicrobial Factors in Mouse Salivary Glands

Abstract

The surfaces of oral mucosa are protected from infections by antimicrobial proteins and natural immunoglobulins that are constantly secreted in saliva, serving as principal innate immune defense in the oral cavity. MyD88 is an important adaptor protein for signal transduction downstream of Toll-like receptors and TACI, receptors for regulation of innate immunity and B cell responses, respectively. Although MyD88-mediated signaling has a regulatory role in the intestinal mucosal immunity, its specific role in the oral cavity has remained elusive. In the present study, we assessed the influence of MyD88 deficiency on the oral innate defense, particularly the expression of antimicrobial proteins in salivary glands and production of salivary basal immunoglobulins, in mice. Microarray analysis of the whole tissues of submandibular glands revealed that the expression of several genes encoding salivary antimicrobial proteins, such as secretory leukocyte peptidase inhibitor (SLPI), S100A8, and lactotransferrin, was reduced due to MyD88 deficiency. Histologically, SLPI-expressing acinar cells were evidently decreased in the glands from MyD88 deficient mice compared to wild-type mice. Flow cytometric analysis revealed that B cell populations, including B-1 cells and IgA+ plasma cells, residing in submandibular glands were increased by MyD88 deficiency. The level of salivary anti-phosphorylcholine IgA was elevated in MyD88 deficient mice compared to wild-type mice. Thus, this study provides a detailed description of the effect of MyD88 deficiency on expression of several salivary antimicrobial factors in mice, illustrating the role for MyD88-mediated signaling in the innate immune defense in the oral cavity.

MyD88 signaling causes autoimmune sialadenitis through formation of high endothelial venules and upregulation of LTβ receptor-mediated signaling

“…Spleen B220 + cells were slightly increased in Myd88 -deficient mice (Fig. 2a ), but similar observations have been reported in other mouse strains 28 , 29 . T cell subsets in the spleen and SGALNs were almost identical in Myd88 +/+ and Myd88 −/− NOD mice (Fig.…”

“…NOD/ShiLtJ (NOD) mice were obtained from Charles River Laboratories, Japan (Yokohama, Japan). B6- Myd88 −/− mice were described previously 29 . A congenic strain, NOD.B6- Myd88 −/− , was generated by crossing NOD with B6- Myd88 −/− mice.…”

Human salivary gland cells express bradykinin receptors that modulate the expression of proinflammatory cytokines

“…However, it is interesting that bradykinin shows a similar proinflammatory effect in the exocrine system. Salivary glands are involved in the local immune reactions with their innate immunity-related receptors, including TLRs (39)(40)(41). Thus, further investigation of the bradykinin-mediated induction of salivary cytokines on the basis of our findings will eventually contribute to understanding the changes in salivary functions mediated by pathological conditions such as inflammation and angioedema.…”

B‐1 cells as a source of IgA

“…IgA secretion by B‐1 cells was also investigated in extraperitoneal or pleural localizations, namely in lacrimal and salivary glands . Phenotypical analysis of mononuclear cells isolated from lacrimal glands showed that approximately 4% of cells were IgA + B cells, and IgA + B cells mainly belonged to the B‐1 lineage (B220 low ) as defined by CD5 surface expression .…”

“…Another study addressed the impact of myeloid differentiation primary response gene 88 (MyD88) deficiency on mucosal immunity by analyzing salivary glands in Myd88 knockout mice . Both B‐1a and B‐1b cells were increased in the submandibular glands of Myd88 knockout compared to wild‐type mice, but no differences were detected in the number of B‐2 cells.…”