JEM流感病毒繼發(fā)感染模型肺泡巨噬細(xì)胞清除解決方案

中文摘要：

在流感病毒繼發(fā)感染期間，漿細(xì)胞 （PCs） 在肺內(nèi)發(fā)育，提供局部抗體來(lái)源。然而，調(diào)節(jié)這一過(guò)程的場(chǎng)所和機(jī)制定義不明確。在這里，我們表明，雖然循環(huán)記憶 B 細(xì)胞在再攻擊期間進(jìn)入肺部并在誘導(dǎo)性支氣管相關(guān)淋巴組織 （iBALTs） 內(nèi)被激活，但常駐記憶 B （BRM） 細(xì)胞反應(yīng)更早，并且它們的激活發(fā)生在不同的生態(tài)位：直接靠近受感染的肺泡。這個(gè)過(guò)程需要 NK 細(xì)胞，但在很大程度上獨(dú)立于 CD4 和 CD8 T 細(xì)胞。在沒有同源抗原的情況下，含有 ssRNA 的病毒樣顆粒誘導(dǎo)的先天刺激觸發(fā)了 BRM 細(xì)胞分化，表明激活閾值較低。相比之下，iBALTs 中 PC 的擴(kuò)增需要更長(zhǎng)的時(shí)間來(lái)發(fā)展，并且嚴(yán)重依賴于 CD4 T 細(xì)胞。我們的工作表明，空間上不同的機(jī)制進(jìn)化為支持肺部繼發(fā)性 PC 反應(yīng)，并揭示了 BRM 細(xì)胞作為肺泡守護(hù)者的特殊功能。

英文摘要：

During secondary infection with influenza virus, plasma cells (PCs) develop within the lung, providing a local source of antibodies. However, the site and mechanisms that regulate this process are poorly defined. Here, we show that while circulating memory B cells entered the lung during rechallenge and were activated within inducible bronchus-associated lymphoid tissues (iBALTs), resident memory B (BRM) cells responded earlier, and their activation occurred in a different niche: directly near infected alveoli. This process required NK cells but was largely independent of CD4 and CD8 T cells. Innate stimuli induced by virus-like particles containing ssRNA triggered BRM cell differentiation in the absence of cognate antigen, suggesting a low threshold of activation. In contrast, expansion of PCs in iBALTs took longer to develop and was critically dependent on CD4 T cells. Our work demonstrates that spatially distinct mechanisms evolved to support pulmonary secondary PC responses, and it reveals a specialized function for BRM cells as guardians of the alveoli.

論文信息：

論文題目： Regulation of pulmonary plasma cell responses during secondary infection with influenza virus

期刊名稱：JEM- J Exp Med

時(shí)間期卷： J Exp Med (2024) 221 (7): e20232014.

在線時(shí)間：2024年4月25日

DOI： doi.org/10.1084/jem.20232014

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于JEM：

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes的材料和方法：

JEM流感病毒繼發(fā)感染模型肺泡巨噬細(xì)胞清除解決方案

Clodronate liposomes (SKU: C-005) and PBS liposomes(SKU: P-005) were commercially available and purchasedfrom Liposoma BV . The concentration of the clodronatein the suspension was 5 mg/ml. Liposome suspensions were injected directly without any further dilutions.  Alveolar macrophages were depleted using IN administration of clodronated liposomes (CLL). 45 μl dosage of Clodrosome (Liposoma BV) was administered IN twice 6 days prior to rechallenge and twice 3 days before rechallenge. The selective depletion of alveolar macrophages using this approach was based on previous works (Leemans et al., 2001) and was optimized in our own hands as described in our recent publication (MacLean et al., 2022). It should be noted that we cannot exclude the possibility that small amounts of CLL that may not been sufficient to kill interstitial phagocytes have reached the parenchyma, potentially compromising neutrophil functionality (Culemann et al., 2023).