Bcl-6 expression by CD4 < sup > + < /sup > T cells determines concomitant immunity and host resistance across distinct parasitic infections

Mucosal Immunol. 2023 Aug 31:S1933-0219(23)00066-1. doi: 10.1016/j.mucimm.2023.08.004. Online ahead of print.ABSTRACTCD4+ T cells consist of multiple subtypes, defined by expression of lineage-specific transcription factors, that contribute to the control of infectious diseases by providing help to immune and non-immune target cells. In the current study, we examined the role of B cell lymphoma (Bcl)-6, a transcriptional repressor and master regulator of T follicular helper cell differentiation, in T cell-mediated host defense against intestinal and systemic parasitic infections. We demonstrate that while Bcl-6 expression by CD4+ T cells is critical for antibody-mediated protective immunity against secondary infection with the nematode Heligmosoides polygyrus bakeri (Hpb), it paradoxically compromises worm expulsion during primary infection by limiting the generation of IL-10-producing Gata3+ Th2 cells. Enhanced worm expulsion in the absence of Bcl-6 expressing T cells was associated with amplified intestinal goblet cell differentiation and increased generation of alternatively activated macrophages, effects that were reversed by neutralization of IL-10 signals. An increase in IL-10 production by Bcl-6-deficient CD4+ T cells was also evident in the context of systemic Leishmania donovani infection but, in contrast to Hpb infection, compromised Th1-mediated liver macrophage activation and increased susceptibility to this distinct parasitic challenge. Collectively, our studies ...
Source: Cancer Control - Category: Cancer & Oncology Authors: Source Type: research