Histiocytes are white blood cells of the monocytic lineage and include macrophages and dendritic cells. In patients with a variety of infectious and noninfectious inflammatory disorders, histiocytes can engulf nonapoptotic leukocytes and nonsenescent erythrocytes and thus become hemophagocytes. We report here the identification and characterization of splenic hemophagocytes in a natural model of murine typhoid fever. The development of a flow-cytometric method allowed us to identify hemophagocytes based on their greater than 6N (termed 6N+) DNA content. Characterization of the 6N+ population from infected mice showed that these cells consist primarily of macrophages rather than dendritic cells and contain T lymphocytes, consistent with hemophagocytosis. Most 6N+ macrophages from Salmonella enterica serovar Typhimurium-infected mice contain intact DNA, consistent with hemophagocytosis. In contrast, most 6N+ macrophages from control mice or mice infected with a different bacterial pathogen, Yersinia pseudotuberculosis, contain damaged DNA. Finally, 6N+ splenic macrophages from S. Typhimurium-infected mice express markers consistent with an anti-inflammatory M2 activation state rather than a classical M1 activation state. We conclude that macrophages are the predominant splenic hemophagocyte in this disease model but not in Y. pseudotuberculosis-infected mice. The anti-inflammatory phenotype of hemophagocytic macrophages suggests that these cells contribute to the shift from acute to chronic infection.
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机译：组织细胞是单核细胞系的白细胞，包括巨噬细胞和树突状细胞。在患有多种感染性和非感染性炎症性疾病的患者中，组织细胞会吞噬非凋亡性白细胞和非衰老性红细胞，从而变成噬血细胞。我们在这里报告鼠伤寒热的自然模型中的脾嗜血细胞的鉴定和表征。流式细胞术方法的发展使我们能够基于大于6N（称为6N +）的DNA含量来鉴定血细胞。对受感染小鼠的6N +群体的鉴定表明，这些细胞主要由巨噬细胞而非树突状细胞组成，并含有T淋巴细胞，与吞噬作用一致。鼠伤寒沙门氏菌感染鼠伤风的大多数6N +巨噬细胞均含有完整的DNA，与噬血细胞作用一致。相比之下，大多数来自对照小鼠或感染了不同细菌病原体假单胞菌耶尔森氏菌的小鼠的6N +巨噬细胞均含有受损的DNA。最后，来自 S 的6N +脾巨噬细胞。感染鼠伤寒的小鼠表达的标志物与抗炎M2激活状态而非经典M1激活状态一致。我们得出的结论是，巨噬细胞是这种疾病模型中的主要脾脏噬血细胞，而不是在假结核杆菌感染的小鼠中。噬血细胞巨噬细胞的抗炎表型表明，这些细胞有助于从急性感染向慢性感染的转变。
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