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Modulation of Interferon Signaling by Streptococcus sanguinis Vesicles: A New Mechanism of Oral Immune Regulation

Award Number: R21DE035757
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2026
PERIOD OF PERFORMANCE END DATE: 07/14/2028

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Modulation of Interferon Signaling by Streptococcus sanguinis Vesicles: A New Mechanism of Oral Immune Regulation - Project Summary Emerging evidence suggests that commensal bacteria in the oral cavity may influence adaptive immune responses, yet the underlying mechanisms remain largely undefined. Our recent work suggests that extracellular membrane vesicles (EMVs) from the oral commensal Streptococcus sanguinis (Ss) selectively inhibit type I interferon signaling in oral epithelial cells without broadly suppressing inflammatory cytokine responses. Given the central role of dysregulated interferon signaling in autoimmune diseases such as systemic lupus erythematosus (SLE), Behçet disorder and primary Sjögren’s syndrome (pSS), this project investigates the novel immunomodulatory potential of S. sanguinis EMVs. We aim to define the molecular mechanism of interferon pathway inhibition, focusing on the predicted subtilisin-like protease SSA1882, enriched in Ss EMVs. Using biochemical, proteomic, and transcriptomic approaches, we will test if SSA1882 directly cleaves interferons to disrupt downstream JAK/STAT signaling in gingival and salivary epithelial cells. We will also assess whether this phenotype is unique to Ss or shared among other oral Streptococci. Finally, we will explore the systemic effects of Ss EMVs on adaptive immunity by evaluating B and T cell activation and differentiation in human peripheral blood mononuclear cells. This project is innovative in its focus on Gram-positive bacterial vesicles and their potential to modulate host immune pathways relevant to autoimmune pathology. By elucidating how oral commensal-derived EMVs regulate interferon signaling, our study may uncover previously unrecognized connections between oral microbial ecology and adaptive immune regulation, with implications for novel therapeutic approaches targeting autoimmune diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $429,000 )
2026	2026	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Oral Diseases and Disorders Research	000	1	7/17/2026	NEW	$429,000
														Subtotal = $429,000

Grand Total All Awards = $429,000

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Modulation of Interferon Signaling by Streptococcus sanguinis Vesicles: A New Mechanism of Oral Immune Regulation

Award Number: R21DE035757

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/15/2026

PERIOD OF PERFORMANCE END DATE: 07/14/2028

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