Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St., Boston, MA 02215, United States.
Department of Microbiology & Immunology, Mbeya College of Health and Allied Sciences, Hospital Hill Rd, University of Dar es Salaam, Mbeya 53107, Tanzania.
J Leukoc Biol. 2023 Oct 26;114(5):459-474. doi: 10.1093/jleuko/qiad091.
Cytomegalovirus (CMV) is a ubiquitous herpes virus that infects most humans, thereafter persisting lifelong in tissues of the host. It is a known pathogen in immunosuppressed patients, but its impact on immunocompetent hosts remains less understood. Recent data have shown that CMV leaves a significant and long-lasting imprint in host immunity that may confer some protection against subsequent bacterial infection. Such innate immune activation may come at a cost, however, with potential to cause immunopathology. Neutrophils are central to many models of immunopathology, and while acute CMV infection is known to influence neutrophil biology, the impact of chronic CMV infection on neutrophil function remains unreported. Using our murine model of CMV infection and latency, we show that chronic CMV causes persistent enhancement of neutrophil oxidative burst well after resolution of acute infection. Moreover, this in vivo priming of marrow neutrophils is associated with enhanced formyl peptide receptor expression, and ultimately constitutive c-Jun N-terminal kinase phosphorylation and enhanced CD14 expression in/on circulating neutrophils. Finally, we show that neutrophil priming is dependent on viral load, suggesting that naturally infected human hosts will show variability in CMV-related neutrophil priming. Altogether, these findings represent a previously unrecognized and potentially important impact of chronic CMV infection on neutrophil responsiveness in immunocompetent hosts.
巨细胞病毒（CMV）是一种普遍存在的疱疹病毒，感染大多数人类，此后在宿主组织中终身持续存在。它是免疫抑制患者的已知病原体，但对免疫功能正常宿主的影响仍知之甚少。最近的数据表明，CMV 在宿主免疫中留下了显著且持久的印记，这可能为随后的细菌感染提供一定的保护。然而，这种先天免疫激活可能会带来代价，并有潜在的免疫病理学风险。中性粒细胞是许多免疫病理学模型的核心，虽然急性 CMV 感染已知会影响中性粒细胞生物学，但慢性 CMV 感染对中性粒细胞功能的影响仍未被报道。我们使用 CMV 感染和潜伏的小鼠模型表明，慢性 CMV 在急性感染消退后很久仍会持续增强中性粒细胞的氧化爆发。此外，这种骨髓中性粒细胞的体内预激活与增强的甲酰肽受体表达有关，最终导致循环中性粒细胞中组成性 c-Jun N 端激酶磷酸化和 CD14 表达增强。最后，我们表明中性粒细胞的预激活依赖于病毒载量，这表明自然感染的人类宿主在 CMV 相关的中性粒细胞预激活方面会表现出可变性。总之，这些发现代表了慢性 CMV 感染对免疫功能正常宿主中性粒细胞反应性的一个以前未被认识到的潜在重要影响。
