Technology Bundle ID: TAB-3343

Methods for Dagnosing and Treating Mycobacterium tuberculosis (Mtb) Infection through Detection of CD153 Expression Level.

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Primary Inventors: 
Daniel Barber (NIAID)
Co-Inventors: 
Keith Kauffman (NIAID), Michelle Sallin (NIAID)
Institute or Center: 
NIAID

Mycobacterium tuberculosis (Mtb) infection continues to be the leading cause of death due to a single infectious agent and poses significant global health challenges. Past research has shown that CD4 T cells are essential for resistance to Mtb infection, and for decades it has been thought that IFN(γ) production is the primary mechanism of CD4 T cell-mediated protection.

NIAID researchers have discovered that the expression of TNF superfamily molecule CD153 (TNSF8) is required for control of the pulmonary Mtb infection by CD4 T cells. The results have shown that, in Mtb infected mice, CD153 expression is highest on Ag-specific Th1 cells in the lung tissue parenchyma. On the contrary, CD153 deficient mice have developed high pulmonary bacterial loads and succumb early to Mtb infection. In Mtb infected non-human primates, CD153 expression is much higher on Ag-specific CD4 T cells in the airways compared to the blood, and the frequency of Mtb-specific CD153-expressing CD4 T cells inversely correlates with bacterial loads in granulomas. Further, in Mtb infected humans, CD153 defines a subset of highly polyfunctional Mtb-specific CD4 T cells that are much more abundant in individuals with controlled latent Mtb infection compared to those with active TB. Since the expression of CD153 by CD4 T cells is a major immune mechanism of host protection against Mtb infection, the discovery can be used to effectively diagnose and treat Mtb infections in the future.

Applications:
  • Mycobacterium tuberculosis diagnostic that measures the production of CD153 as an indicator of the disease and its severity
  • A companion diagnostic can be used to determine the effectiveness of a vaccine against a Mycobacterium tuberculosis infection in a subject
  • Therapeutic use to treat Mycobacterium tuberculosis in a subject
Advantages:
  • Ability to be used as a target for Mtb diagnostics and therapeutics

Patents

PCT Application PCT/US2019/019164
Filed on 2019-02-22
US Application 16/971,144
Filed on 2020-08-19
US Application 62/633,816
Filed on 2018-02-22

Publications

Sallin, Michelle A., et al.
PMID: 30202016

Updated

Nov 9, 2018

Data Source: 
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