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Role of Macrophage Migration Inhibitory Factor induced NETosis in regulating CDI severity

Award Number: F31AI200192
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/10/2026
PERIOD OF PERFORMANCE END DATE: 12/09/2027

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Role of Macrophage Migration Inhibitory Factor induced NETosis in regulating CDI severity - PROJECT SUMMARY Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections in the United States. The current primary treatment strategy for this infection is antibiotics. However, patients who receive antibiotics are at risk of recurrent CDI, highlighting the need for novel host-mediated therapies. Our lab has shown that neutrophils worsen C. difficile toxin-induced intestinal epithelial cell (IEC) damage, and transcriptomic data show that genes associated with neutrophil extracellular trap formation (NETosis) are upregulated in blood neutrophils after CDI. Furthermore, our novel preliminary observation shows that the presence of C. difficile bacteria induces NET formation in vitro. Additionally, we have previously demonstrated that macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, plays a detrimental role in CDI pathogenesis. However, the underlying mechanisms by which MIF mediates CDI severity remain unknown. Published studies have shown that MIF induces NETosis. Aberrant NETs cause tissue damage in various pathologies. Therefore, in this project, we aim to determine whether NETosis leads to collateral tissue damage in CDI and examine MIF's role as an upstream driver of this response. To investigate this objective, in Aim 1, we will determine whether NETs directly contribute to IEC damage during CDI by promoting apoptosis and disruption of tight junction proteins. Aim 2 will then investigate whether MIF induces NETosis via an NADPH oxidase- dependent pathway during CDI. By elucidating the role of MIF-mediated NETosis in CDI, we aim to determine whether the MIF-NETs axis represents a viable host-derived therapeutic target for CDI.


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 = $50,112 )
2026	2026	CINCINNATI UNIV OF	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Allergy and Infectious Diseases Research	000	1	6/11/2026	NEW	$50,112
														Subtotal = $50,112

Grand Total All Awards = $50,112

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Role of Macrophage Migration Inhibitory Factor induced NETosis in regulating CDI severity

Award Number: F31AI200192

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/10/2026

PERIOD OF PERFORMANCE END DATE: 12/09/2027

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