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Although dendritic cells (DCs) are known to be involved in disease progression and immune responses during S. mutans infection, little is known about the component of S. mutans responsible for the DC responses. Although the mannose phosphotransferase system (Man-PTS) is the primary sugar transporter of S. mutans, it is also a potential virulence factor. Since Man-PTS subunit IID (ManIID) embedded on the bacterial membrane is indispensable for Man-PTS function, we investigated its role in the maturation and activation of DCs stimulated with a ManIID-deficient strain (\u0394pts) of S. mutans and recombinant ManIID (rManIID) protein. When mouse bone marrow-derived DCs were treated with heat-killed S. mutans wild-type (WT) or \u0394pts, bacterial adherence and internalization of \u0394pts were lower than those of WT. Moreover, the heat-killed S. mutans \u0394pts strain was inferior to the wild-type in inducing expression of phenotypic maturation markers, such as CD80, CD86, MHC-I, and MHC-II, and proinflammatory cytokine, IL-6. In line with the trends in marker expression, the endocytic capacity of DCs treated with the \u0394pts strain was comparable to that of untreated DCs whereas DCs treated with the WT strain dose-dependently lost their endocytic capacity. Furthermore, rManIID dose-dependently promoted both phenotypic maturation marker expression and IL-6 production by DCs. Collectively, these results demonstrate that ManIID plays a crucial role in the adhesion and internalization of S. mutans into DCs and is one of the major immune-stimulating agents responsible for maturation and activation of DCs during S. mutans infection.<\/jats:p>","DOI":"10.71150\/jm.2505014","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T01:08:06Z","timestamp":1761786486000},"page":"e2505014","update-policy":"https:\/\/doi.org\/10.71150\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mannose phosphotransferase system subunit IID of Streptococcus mutans elicits maturation and activation of dendritic 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