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Induction of myeloid-derived suppressor cells (MDSCs) by mycobacteria vaccines

Subject Area Immunology
Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
Term from 2020 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 442275424
 
Final Report Year 2024

Final Report Abstract

Tuberculosis remains one of the deadliest infectious diseases worldwide. Despite the heterologous BCG vaccine, which shows a limited protection, a Mycobacterium tuberculosis (Mtb)-based homologous vaccine is not available to date. We found earlier that double immunization with heat-killed Mtb massively induced monocytic myeloid-derived suppressor cells (M-MDSC) in mice. Our new results indicated that induction of M-MDSC is not an exclusive feature of Mtb, but Mtb appears quantitatively superior over other bacteria, including Mycobacterium bovis, Mycobacterium smegmatis, Listeria monocytogenes. In contrast, BCG vaccination did not generate M-MDSC or other myeloid cell types under any condition tested. Surprisingly, Mtb-immunized mice with heterologous BCG infection resulted in protection, despite elevated M- MDSC frequencies. Remarkably, mice immunized with the same dose of BCG and then infected with homologous BCG showed no protection. These results provide new insights into the relationship between M-MDSC induction, T cell response, and protection from disease after homologous versus heterologous vaccination.

Publications

  • 18th International Congress of Immunology (IUIS 2023), Cape Town, South Africa, 27 Nov - 2 Dec 2023. Opposite capacities of Mtb and BCG heat-killed vaccines for the induction of monocytic myeloid-derived suppressor cells in mice
    Arpa Aintablian, Laura Cyran & Manfred B. Lutz
  • European Macrophage and Dendritic Cell Society (EMDS), Gent, Belgium, 18-20 Oct 2023. Opposite capacities of Mtb and BCG heat-killed vaccines for the induction of monocytic myeloid-derived suppressor cells in mice
    Arpa Aintablian1, Laura Cyran1 & Manfred B. Lutz1
  • M-MDSC in vitro generation from mouse bone marrow with IL-3 reveals high expression and functional activity of arginase 1. Frontiers in Immunology, 14.
    Aintablian, Arpa; Strozniak, Sandra; Heuer, Marion & Lutz, Manfred B.
  • 7th European Congress of Immunology (ECI), Dublin, Ireland, 1-4 Sep 2024. Heterologous Bacillus Calmette-Guérin infection reverts the monocytic myeloid-derived suppressor cell phenotype induced by prior Mycobacterium tuberculosis immunization into innate and adaptive effector cell responses
    Arpa Aintablian, Laura Cyran, Haisam Al Attar, Christoph Schön, Nelita du Plessis, Gerhard Walzl, Ulrich E. Schaible & Manfred B. Lutz
  • Myeloid-derived suppressor cell induction by IL-3 in vitro and by mycobacterial vaccination in vivo. PhD thesis at the University of Würzburg.
    Arpa Aintablian
  • Symposium “Infection and Immune Defense”, Rothenfels Castle, Germany, 4-6 Mar 2024. Heterologous BCG infection reverts the M-MDSC phenotype induced by prior Mtb immunization into innate and adaptive effector cell responses
    Arpa Aintablian, Laura Cyran, Christoph Schoen, Nelita Du Plessis, Gerhard Walzl, Ulrich Schaible & Manfred B. Lutz
 
 

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