Backup mandate Research Council: Unraveling the mechanisms implicated in malignant leukemia B cell apoptosis following African trypanosome infection.

Project Details

Description

Our laboratory has gathered undoubted evidence demonstrating the detrimental role of African trypanosome infection on B cell biology. For example, these parasites are able to wipe out B cell-associated memory compartments against unrelated pathogens, rendering the host as susceptible as a naïve one. More recently, a “beneficial” role of trypanosome infection on the outcome of B cell-mediated rheumatoid arthritis and B cell cancer was also identified. Although apoptosis seems a major driving force leading to B cell dysfunction, the exact mechanism(s) induced by the parasite to undermine detrimental B cell responses are still being explored. This research proposal will use this parasite-associated peculiar property on B cells as a tool to identify the mechanisms implicated in malignant B cell chronic lymphocytic leukemia (B-CLL) apoptosis. CLL represents
30% of adult leukemia, and is still incurable. To achieve this goal, we will focus on i) characterizing B-CLL apoptotic mechanisms via activation of cGAS, and ii) identifying the host immunity-derived cellular and molecular mechanisms leading to apoptosis of B-CLL cells, with an emphasis on the role of CD4+ T cells and IFNɣ pro- inflammatory cytokine in response to African trypanosome infection.
A thorough understanding of the molecular mechanisms implicated in these apoptotic processes might potentially lead to the development of a new intervention strategy against B cell-related cancer.
AcronymOZR3833
StatusActive
Effective start/end date1/11/2131/10/22

Flemish discipline codes

  • Infectious diseases
  • Parasitology
  • Adaptive immunology
  • Inflammation
  • Cancer therapy

Keywords

  • Parasitic African trypanosome infection
  • malignant leukemic B cell apoptosis
  • inflammatory- mediated immunopathologies