Persistent Leishmania donovani infection is characterized by chronic inflammation, immune suppression, and splenomegaly. We have previously reported that the transcription factor interferon regulatory factor 5 (IRF-5) is largely responsible for inducing the inflammatory response and maintaining protective Th1 cells following L. donovani inoculation in mice. However, the cellular source responsible for these effects is yet unknown. In this study, we investigated the role of IRF-5 in myeloid cells during experimental visceral leishmaniasis (VL). First, we show that the LysM-Cre mouse model is not suited for investigating gene expression in splenic myeloid cells during experimental VL. Using the Cd11c-Cre mouse model, we demonstrate that Irf5 expression in CD11c+ cells (monocytes, dendritic cells, activated macrophages) is essential for inducing splenomegaly and for recruiting myeloid cells to the spleen, but it is not required for the development or maintenance of parasite-specific IFNγ-producing CD4 T cells. CD11c-specific Irf5 -/- mice are more resistant to L. donovani infection, suggesting that the induction of splenomegaly is detrimental to the host.

中文翻译：

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髓样细胞中IRF-5的表达对于多诺氏乳杆菌感染小鼠的脾肿大是必需的。

持续性利什曼原虫多诺万尼感染的特征在于慢性炎症，免疫抑制和脾肿大。我们以前曾报道过，转录因子干扰素调节因子5（IRF-5）在小鼠中感染了诺瓦氏乳杆菌后，在诱导炎症反应和维持保护性Th1细胞方面起着主要作用。然而，负责这些作用的细胞来源仍是未知的。在这项研究中，我们调查了IRF-5在实验性内脏利什曼病（VL）期间在髓样细胞中的作用。首先，我们显示LysM-Cre小鼠模型不适合用于研究实验性VL期间脾髓样细胞中的基因表达。使用Cd11c-Cre小鼠模型，我们证明了Irf5在CD11c +细胞（单核细胞，树突状细胞，活化的巨噬细胞）对于诱导脾肿大和将骨髓细胞募集到脾脏是必不可少的，但对于产生或维持寄生虫特异性产生IFNγ的CD4 T细胞则不是必需的。CD11c特异性Irf5-/-小鼠对多诺氏乳杆菌感染更具抵抗力，这表明脾肿大的诱导对宿主有害。