Redressing the Balance Against B Regulatory Cells: Novel Immunotherapeutic Target in Leishmaniasis.

Leishmania parasite adeptly evades the host's immune defences by infiltrating macrophages, exploiting apoptotic processes for further dissemination. Among the host's strategies to counter parasitic propagation, the pivotal role of B-cells, specifically B regulatory (Breg) cells, emerges. Recent evidence from in vitro and in vivo studies has thrust Breg cells into the spotlight, attributed to their IL-10 secretion and antigen presentation. The escalated IL-10 production coupled with decreased Th1 response provides a conducive milieu for parasitic proliferation within host cells. This abundance of IL-10, from Breg cells and other immune sources, impedes T cell differentiation into Th1, Th2 and Th17 subsets. Moreover, IL-10 obstructs CD8+ T cell differentiation into cytotoxic T cells, heightening the host's susceptibility to infections. Breg cells are also implicated in the production of IL-35, which in turn mediates the conversion of B cells into Breg and IL-35+ Breg cells and helps Leishmania to evade the immune response. Notably, recent data underscore the potential of B cell reprogramming via BTK and MEK inhibitors, offering a novel immunomodulation strategy. This approach presents a novel avenue for curbing Breg cells, potentially hindering prolonged BCR signalling. Although promising for Leishmania infection immunotherapy, a comprehensive understanding of IL-10-producing B cells' exact role demands further exploration. Developing targeted strategies to modulate Breg cell function could revolutionise Leishmania treatment, enhancing patient outcomes. Understanding Breg cells' role offers promising avenues for precise immunotherapy against this challenging infection.