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Oral commensal fungi and structural immunity

Award Number: R01DE031382
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: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Oral commensal fungi and structural immunity - PROJECT SUMMARY While the fungus Candida albicans has largely been studied as a pathogen, its primary lifestyle is as a commensal on mucosal surfaces, including the oral cavity. Microorganisms that occupy mucosal surfaces are critical for appropriately tuning immune responses to ensure efficient responses to invading pathogens while limiting responses directed towards host tissues. In this context, commensal fungi play important roles in host immunity and inflammation. For instance, C. albicans colonization induces cross-reactive T cells and innate memory in immune cells, a mechanism termed trained immunity. Accumulating evidence from our group and others have convincingly demonstrated that oral commensal colonization with C. albicans induces specific immune responses, therefore contributing to mucosal immune system plasticity. However, the fundamental immunological consequences of oral C. albicans colonization are still not well understood. Host tissues maintain traces or memory after microorganism encounter that extend beyond adaptive responses of T and B cells. These changes include profound structural remodeling and epigenetic alterations. ‘Structural immunity’, the immune response within a tissue framework created by structural cells, such as endothelial and epithelial cells, is essential for maintaining tolerance and the development of appropriate protective and controlled immune responses. In probing for structural processes that maintain effective mucosal immunity in the oral cavity, we identified two mechanisms which are tuned during oral commensal C. albicans colonization, oral epithelial proliferation and angiogenesis. Our central hypothesis is that commensal C. albicans exposure in the oral cavity establishes mucosal ‘structural immunity’ by inducing oral epithelial trained immunity, epithelial remodeling, and angiogenesis. These tissue remodeling and innate priming events serve to maintain effective mucosal immunity, thus preventing oral fungal outgrowth of this important commensal organism. This proposal will evaluate the molecular mechanisms by which oral commensal C. albicans induce epithelial proliferation (Aim 1), and angiogenesis (Aim1 and 2). In Aim1 we will delineate the role of IL-22 in mediating oral structural immunity in response to commensal C. albicans colonization. In Aim 2 we will determine the role of VEGF as a mediator of trained and structural immunity in the oral cavity.


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: 2025 ( Subtotal = $507,596 )
2025	2025	LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER	1124 W CARSON ST BLDG MRL	TORRANCE	CA	90502	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	4	5/30/2025	NON-COMPETING CONTINUATION	$507,596
														Subtotal = $507,596

Issue Date FY: 2024 ( Subtotal = $497,444 )
2024	2024	LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER	1124 W CARSON ST BLDG MRL	TORRANCE	CA	90502	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	3	5/29/2024	NON-COMPETING CONTINUATION	$497,444
														Subtotal = $497,444

Issue Date FY: 2023 ( Subtotal = $513,239 )
2023	2023	LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER	1124 W CARSON ST	TORRANCE	CA	90502	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	2	5/15/2023	NON-COMPETING CONTINUATION	$513,239
														Subtotal = $513,239

Issue Date FY: 2022 ( Subtotal = $519,964 )
2022	2022	LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER	1124 W CARSON ST	TORRANCE	CA	90502	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	1	6/27/2022	NEW	$519,964
														Subtotal = $519,964

Grand Total All Awards = $2,038,243

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Oral commensal fungi and structural immunity

Award Number: R01DE031382

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: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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