Publications by authors named "Vinzeigh N Leukes"

3 Publications

  • Page 1 of 1

Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis.

Cell Immunol 2021 Jun 8;364:104359. Epub 2021 Apr 8.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address:

Conventional anti-tuberculosis (TB) therapies comprise lengthy antibiotic treatment regimens, exacerbated by multi-drug resistant and extensively drug resistant mycobacterial strains. We assessed the ability of all-trans retinoic acid (ATRA), as repurposed compound serving as host-directed therapy (HDT), to counteract the suppressive effects of myeloid-derived suppressor cells (MDSCs) obtained from active TB cases (untreated or during week one of treatment) on T-cell responsiveness. We show for the first time that MDSCs suppress non-specific T-cell activation and production of interleukin (IL)-2, IL-4, IL-13 and GM-CSF via contact-dependent mechanisms. ATRA treatment decreases MDSC frequency, but fails to mature MDSCs to non-suppressive, terminally differentiated myeloid cells and does not restore T-cell function or cytokine production in the presence of MDSCs. The impact of ATRA treatment on improved immunity, using the concentration tested here, is likely to be minimal, but further identification and development of MDSC-targeting TB host-directed therapies are warranted.
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http://dx.doi.org/10.1016/j.cellimm.2021.104359DOI Listing
June 2021

Isolation and Functional Characterization of Myeloid-Derived Suppressor Cells in Infections Under High Containment.

Methods Mol Biol 2021 ;2236:129-156

Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.

The current absence of markers unique to MDSC, particularly those expanded during human infection, necessitate concurrent demonstration of their suppressive capacity to ensure unequivocal identification. This is further complicated by the array of heterogeneous markers used to characterize MDSC in various conditions and models. Standardization of phenotypic and functional characterization, as well as isolation, from infectious biological samples of patients, are critical for accurately reporting MDSC dynamics, function, organ abundance, and establishment of their therapeutic value in infectious diseases. To illustrate, we report on our established method for MDSC isolation from bronchoalveolar lavage fluid and peripheral blood of pulmonary TB patients, as well as functional impact on T cells by measuring T cell activation, proliferation, and cytokine production.
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http://dx.doi.org/10.1007/978-1-0716-1060-2_12DOI Listing
March 2021

Mycobacterium tuberculosis and myeloid-derived suppressor cells: Insights into caveolin rich lipid rafts.

EBioMedicine 2020 Mar 26;53:102670. Epub 2020 Feb 26.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address:

Mycobacterium tuberculosis (M.tb) is likely the most successful human pathogen, capable of evading protective host immune responses and driving metabolic changes to support its own survival and growth. Ineffective innate and adaptive immune responses inhibit effective clearance of the bacteria from the human host, resulting in the progression to active TB disease. Many regulatory mechanisms exist to prevent immunopathology, however, chronic infections result in the overproduction of regulatory myeloid cells, like myeloid-derived suppressor cells (MDSC), which actively suppress protective host T lymphocyte responses among other immunosuppressive mechanisms. The mechanisms of M.tb internalization by MDSC and the involvement of host-derived lipid acquisition, have not been fully elucidated. Targeted research aimed at investigating MDSC impact on phagocytic control of M.tb, would be advantageous to our collective anti-TB arsenal. In this review we propose a mechanism by which M.tb may be internalized by MDSC and survive via the manipulation of host-derived lipid sources.
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http://dx.doi.org/10.1016/j.ebiom.2020.102670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047144PMC
March 2020