本研究探讨了B细胞淋巴瘤（Bcl）-6在T细胞介导的肠道和全身寄生虫感染中的宿主防御作用。CD4+T细胞的Bcl-6表达在对副感染蛔虫Heligmosoides polygyrus bakeri（Hpb）的抗体介导保护性免疫中起关键作用，但却通过限制产生Gata3+Th2细胞中的IL-10来矛盾地影响了初次感染中的虫子排出。在Bcl-6表达T细胞缺失时增强了虫子排出，并伴有肠道粘液细胞的增强分化和替代活化巨噬细胞的增加，这些效应可被中和IL-10信号逆转。Bcl-6缺乏的CD4+T细胞在全身利什曼寄生虫感染背景下的增加IL-10生成也是明显的，然而与Hpb感染相反，这增加了Th1介导的肝脏巨噬细胞活化并增加了对这种不同寄生虫挑战的易感性。综上所述，我们的研究表明，保护免疫性双重感染和致命全身原虫感染的宿主防御途径可能以耐受良好的蛔虫感染的主要抵抗受损为代价。© 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

CD4+ 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 suggest that host defense pathways that protect against parasite superinfection and lethal systemic protozoal infections can be engaged at the cost of compromised primary resistance to well-tolerated helminths.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.