The interplay of protein secretion and lipid virulence factors in host immune suppression by Mycobacterium tuberculosis
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
Mycobacterium tuberculosis (Mtb) infects one-quarter of the global population and causes more deaths annually than any other infectious disease. Despite triggering a strong immune response, Mtb evades and suppresses host immunity, establishing chronic infection. Two critical virulence factors, the ESX-1 type VII secretion system and the mycomembrane lipid phthiocerol dimycocerosate (PDIM), play a key role in this immune modulation, but their precise mechanisms remain unclear. Recent data suggest that ESX-1 and PDIM may functionally intersect, as mutants in these pathways exhibit similar virulence phenotypes. This proposal aims to investigate whether ESX-1 and PDIM operate within the same virulence pathway and how PDIM influences ESX-1. Additionally, we will explore whether their roles in virulence involve suppression of protective Th17 CD4 T cell responses and induction of immunosuppressive type I interferons (IFNs). Aim 1 will test whether ESX-1 and PDIM exhibit epistasis for virulence in mice and define how PDIM impacts ESX-1 function. We hypothesize that PDIM mutants subtly affect ESX-1 activity, which will be tested through epistasis experiments and proteomic profiling of ESX-1 function in PDIM mutants. Aim 2 will investigate whether blocking IL-23 explains the suppression of Th17 differentiation by ESX-1/PDIM mutants. We have shown that these mutants induce higher IL-23 production and a robust Th17 response, suggesting that ESX-1 and PDIM suppress this protective response. We will test the role of IL-23 suppression in Th17 differentiation and perform epistasis testing for CD4 T cell orchestration. Aim 3 will determine whether type I IFN induction is necessary for the virulence of ESX-1 and PDIM mutants. Both factors induce type I IFN, which impairs host responses to Mtb. We will test if type I IFN induction is critical for virulence by evaluating mutant strains in mice lacking type I IFN signaling. These studies will provide valuable insights into Mtb's immune evasion strategies, potentially leading to new therapeutic interventions.
Grant Summary
The interplay of protein secretion and lipid virulence factors in host immune suppression by Mycobacterium tuberculosis is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $757K for university, nonprofit, healthcare org. Applications are due 2031-03-31 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $757K
2031-03-31
- 1Confirm your organization is eligible for The interplay of protein secretion and lipid virulence factors in host immune suppression by Mycobacterium tuberculosis from NIAID - National Institute of Allergy and Infectious Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIAID - National Institute of Allergy and Infectious Diseases before the deadline.
Don't want to draft it yourself?
We'll draft the complete application against NIAID - National Institute of Allergy and Infectious Diseases's requirements, run a quality review, and email you a submission-ready PDF plus an editable Word doc within 5 business days. Most orders deliver in 24-48 hours. Flat $399, any grant size.
AI Requirement Analysis
Detailed requirements not yet analyzed
Have the NOFO? Paste it below for AI-powered requirement analysis.
The interplay of protein secretion and lipid virulence factors in host immune suppression by Mycobacterium tuberculosis: Frequently Asked Questions
Who is eligible for the The interplay of protein secretion and lipid virulence factors in host immune suppression by Mycobacterium tuberculosis?
The interplay of protein secretion and lipid virulence factors in host immune suppression by Mycobacterium tuberculosis is offered by NIAID - National Institute of Allergy and Infectious Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the The interplay of protein secretion and lipid virulence factors in host immune suppression by Mycobacterium tuberculosis provide?
The interplay of protein secretion and lipid virulence factors in host immune suppression by Mycobacterium tuberculosis provides up to $757K per award from NIAID - National Institute of Allergy and Infectious Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the The interplay of protein secretion and lipid virulence factors in host immune suppression by Mycobacterium tuberculosis deadline?
Applications for The interplay of protein secretion and lipid virulence factors in host immune suppression by Mycobacterium tuberculosis are due 2031-03-31 (open). Because deadlines can change, verify the date with the funder, NIAID - National Institute of Allergy and Infectious Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the The interplay of protein secretion and lipid virulence factors in host immune suppression by Mycobacterium tuberculosis?
To apply for The interplay of protein secretion and lipid virulence factors in host immune suppression by Mycobacterium tuberculosis, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAID - National Institute of Allergy and Infectious Diseases.