Brucellosis is a bacterial disease of domestic animals and humans. The pathogenic ability of Brucella organisms relies on their stealthy strategy and their capacity to replicate within host cells and to induce long-lasting infections. Brucella organisms barely induce neutrophil activation and survive within these leukocytes by resisting microbicidal mechanisms. Very few Brucella-infected neutrophils are found in the target organs, except for the bone marrow, early in infection. Still, Brucella induces a mild reactive oxygen species formation and, through its lipopolysaccharide, promotes the premature death of neutrophils, which release chemokines and express “eat me” signals. This effect drives the phagocytosis of infected neutrophils by mononuclear cells that become thoroughly susceptible to Brucella replication and vehicles for bacterial dispersion. The premature death of the infected neutrophils proceeds without NETosis, necrosis/oncosis, or classical apoptosis morphology. In the absence of neutrophils, the Th1 response exacerbates and promotes bacterial removal, indicating that Brucella-infected neutrophils dampen adaptive immunity. This modulatory effect opens a window for bacterial dispersion in host tissues before adaptive immunity becomes fully activated. However, the hyperactivation of immunity is not without a price, since neutropenic Brucella-infected animals develop cachexia in the early phases of the disease. The delay in the immunological response seems a sine qua non requirement for the development of long-lasting brucellosis. This property may be shared with other pathogenic alphaproteobacteria closely related to Brucella. We propose a model in which Brucella-infected polymorphonuclear neutrophils (PMNs) function as “Trojan horse” vehicles for bacterial dispersal and as modulators of the Th1 adaptive immunity in infection.

中文翻译：

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中性粒细胞在布鲁氏菌病中的作用

布鲁氏菌病是家畜和人类的一种细菌性疾病。布鲁氏菌生物的致病能力依赖于它们的隐秘策略以及它们在宿主细胞内复制和诱导长期感染的能力。布鲁氏菌生物体几乎不诱导中性粒细胞活化，并通过抵抗杀微生物机制在这些白细胞内存活。在感染早期，除骨髓外，在靶器官中发现极少数受布鲁氏菌感染的中性粒细胞。还是布鲁氏菌诱导温和的活性氧形成，并通过其脂多糖促进中性粒细胞过早死亡，从而释放趋化因子并表达“吃我”信号。这种效应驱动受感染的中性粒细胞被单核细胞吞噬，这些单核细胞变得对布鲁氏菌复制和细菌分散载体非常敏感。受感染的中性粒细胞过早死亡，没有 NETosis、坏死/肿块或经典的细胞凋亡形态。在中性粒细胞不存在的情况下，Th1 反应加剧并促进细菌去除，表明布鲁氏菌- 感染的中性粒细胞会抑制适应性免疫。在适应性免疫完全激活之前，这种调节作用为细菌在宿主组织中的扩散打开了一个窗口。然而，免疫过度激活并非没有代价，因为中性粒细胞减少的布鲁氏菌感染动物在疾病的早期阶段会出现恶病质。免疫反应的延迟似乎是长期布鲁氏菌病发展的必要条件。这种特性可能与其他与布鲁氏菌密切相关的致病性α变形菌共有。我们提出了一个模型，其中布鲁氏菌-感染的多形核中性粒细胞 (PMN) 作为细菌传播的“特洛伊木马”载体和感染中 Th1 适应性免疫的调节剂。