德国马格德堡大学Andreas J. Müller、Pauline Formaglio等研究人员合作发现，一氧化二氮通过抑制宿主细胞的招募来控制硕大利什曼原虫的增殖。相关论文于2021年10月22日在线发表于国际学术期刊《免疫》。

研究人员表示，一氧化氮（NO）是一个重要的抗菌效应因子，但也通过关闭单核细胞衍生吞噬细胞的招募来防止不必要的组织损伤。细胞内病原体，如硕大利什曼原虫，可以劫持这些细胞作为复制的微环境。因此，NO可能通过限制高效病原体增殖所需细胞微环境的可用性来发挥遏制作用。然而，这种间接作用方式仍有待建立。

通过将数学模型与病原体活力和增殖的双光子生物传感器相结合，研究人员表明，硕大利什曼原虫的低增殖率不是由于NO对病原体的直接影响，而是由于放任增殖的宿主细胞的可用性降低。尽管抑制NO的产生会增加这些细胞的招募，从而增加病原体的增殖，但阻断细胞招募会使NO的作用与病原体的增殖脱钩。因此，NO对硕大利什曼原虫的遏制有两种不同的功能：直接杀伤和限制放任增殖的宿主细胞的供应。

附：英文原文

Title: Nitric oxide controls proliferation of Leishmania major by inhibiting the recruitment of permissive host cells

Author: Pauline Formaglio, Mohamad Alabdullah, Anastasios Siokis, Juliane Handschuh, Ina Sauerland, Yan Fu, Anna Krone, Patricia Gintschel, Juliane Stettin, Sandrina Heyde, Juliane Mohr, Lars Philipsen, Anja Schrder, Philippe A. Robert, Gang Zhao, Sahamoddin Khailaie, Anne Dudeck, Jessica Bertrand, Gerald F. Spth, Sascha Kahlfu, Philippe Bousso, Burkhart Schraven, Jochen Huehn, Sebastian Binder, Michael Meyer-Hermann, Andreas J. Müller

Issue&Volume: 2021-10-22

Abstract: Nitric oxide (NO) is an important antimicrobial effector but also prevents unnecessary tissue damage by shutting down the recruitment of monocyte-derived phagocytes. Intracellular pathogens such as Leishmania major can hijack these cells as a niche for replication. Thus, NO might exert containment by restricting the availability of the cellular niche required for efficient pathogen proliferation. However, such indirect modes of action remain to be established. By combining mathematical modeling with intravital 2-photon biosensors of pathogen viability and proliferation, we show that low L. major proliferation results not from direct NO impact on the pathogen but from reduced availability of proliferation-permissive host cells. Although inhibiting NO production increases recruitment of these cells, and thus pathogen proliferation, blocking cell recruitment uncouples the NO effect from pathogen proliferation. Therefore, NO fulfills two distinct functions for L. major containment: permitting direct killing and restricting the supply of proliferation-permissive host cells.

DOI: 10.1016/j.immuni.2021.09.021

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00406-4