Inflammatory neutrophil responses and T cell activation in ART-treated SIVmac239-infected rhesus macaques.

IF 3.4 3区 医学 Q2 IMMUNOLOGY
Sallie L Fell, Sydney M Nemphos, James E Prusak, Hannah C Green, Jordyn Miller, Samuel Q Rowan, Natalie Valencia, Coty Tatum, Mary B Barnes, Carolina Allers, Sarah Scheuermann, Kelly Goff, Clara Krzykwa, Lori A Rowe, Nicholas J Maness, Matilda J Moström, Tiffany Hensley-McBain, Lara Doyle-Meyers, Amitinder Kaur, Jennifer A Manuzak
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Abstract

Modern antiretroviral therapy (ART) regimens have revolutionized the management of human immunodeficiency virus (HIV) and transformed it from a life-threatening disease to a manageable chronic condition. Despite the durable viral suppression associated with ART adherence, people with HIV (PWH) continue to experience chronic immune activation and inflammation, which has been linked with increased risk of developing non-acquired immunodeficiency syndrome (AIDS) comorbidities, including cardiovascular disease, liver disease, or neurocognitive disorders. Importantly, the mechanisms underlying establishment and maintenance of immune activation in ART-treated PWH remain incompletely defined. Here, we used a nonhuman primate model to evaluate associations between markers of systemic immune activation and peripheral neutrophils in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs), both before and after ART. As expected, peripheral frequencies of activated CD4+ and CD8+ T cells were elevated during acute SIV infection and returned to baseline levels following ART initiation. Neutrophil dynamics were impacted during acute SIV infection, including decreased peripheral neutrophil frequencies, increased neutrophil degranulation, and the potential for increased neutrophil extracellular trap (NET) formation. Treatment with ART mitigated these inflammatory neutrophil effector functions. Finally, frequencies of HLA-DR+ CD4+ and CD8+ T cells were significantly positively correlated with frequencies of inflammatory CD62Ldim neutrophils and plasma levels of myeloperoxidase, a component of neutrophil granules. Taken together, these data indicate that neutrophil activity and systemic T cell activation are correlated during acute SIV and early ART. Our work provides insight into associations between neutrophil dynamics and immune activation during HIV/SIV in the context of ART.

经art治疗的sivmac239感染恒河猴的炎症中性粒细胞反应和T细胞活化
现代抗逆转录病毒疗法彻底改变了人类免疫缺陷病毒(HIV)的管理,并将其从一种危及生命的疾病转变为一种可控制的慢性疾病。尽管与抗逆转录病毒治疗依从性相关的持久病毒抑制,艾滋病毒感染者(PWH)继续经历慢性免疫激活和炎症,这与发生非获得性免疫缺陷综合征(艾滋病)合并症的风险增加有关,包括心血管疾病、肝脏疾病或神经认知障碍。重要的是,在art治疗的PWH中,免疫激活的建立和维持机制仍然不完全明确。在这里,我们使用一个非人灵长类动物模型来评估猴免疫缺陷病毒(SIV)感染的恒河猴(RMs)在抗逆转录病毒治疗前后的全身免疫激活标记物和外周中性粒细胞之间的关系。正如预期的那样,在急性SIV感染期间,激活的CD4+和CD8+ T细胞的外周频率升高,并在ART启动后恢复到基线水平。急性SIV感染期间中性粒细胞动力学受到影响,包括外周中性粒细胞频率降低,中性粒细胞脱颗粒增加,中性粒细胞胞外陷阱(NET)形成增加的可能性。抗逆转录病毒治疗减轻了这些炎症中性粒细胞效应功能。最后,HLA-DR+ CD4+和CD8+ T细胞的频率与炎症性CD62Ldim中性粒细胞的频率和血浆中髓过氧化物酶(中性粒细胞颗粒的一种成分)的水平呈显著正相关。综上所述,这些数据表明中性粒细胞活性和系统性T细胞激活在急性SIV和早期ART期间是相关的。我们的工作提供了在ART背景下HIV/SIV期间中性粒细胞动力学和免疫激活之间关系的见解。
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来源期刊
Journal of immunology
Journal of immunology 医学-免疫学
CiteScore
8.20
自引率
2.30%
发文量
495
审稿时长
1 months
期刊介绍: The JI publishes novel, peer-reviewed findings in all areas of experimental immunology, including innate and adaptive immunity, inflammation, host defense, clinical immunology, autoimmunity and more. Special sections include Cutting Edge articles, Brief Reviews and Pillars of Immunology. The JI is published by The American Association of Immunologists (AAI)
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