关键词: Mycobacterium avium complex pulmonary disease Disease progression Immune profile Single-cell RNA sequencing Treatment outcome

Mesh : Humans Male Female Mycobacterium avium-intracellulare Infection / microbiology Aged Transcriptome Mycobacterium avium Complex / genetics Middle Aged Single-Cell Analysis / methods Leukocytes, Mononuclear / metabolism microbiology Lung Diseases / microbiology genetics Gene Expression Profiling Disease Progression Monocytes / metabolism immunology

来  源:   DOI:10.1038/s41598-024-66523-x   PDF(Pubmed)

Abstract:
Mycobacterium avium complex pulmonary disease (MAC-PD) has a heterogeneous clinical course. However, immune profiles associated with MAC-PD clinical course are limited. We performed single-cell RNA sequencing of peripheral blood mononuclear cells from 21 MAC-PD patients divided into three clinical courses: group A, spontaneous culture conversion; group B, stable disease without antibiotic treatment; and group C, progressive disease with antibiotic treatment. A lower proportion of NK cells and higher proportion of monocytes were noted in group C compared to combined groups A and B. The proportion of classical monocytes was higher in group C compared to groups A and B, while the proportion of non-classical monocytes decreased. EGR1, HSPA1A, HSPA1B, and CD83 were up-regulated in spontaneous culture conversion group A compared to progressive disease group C. Up-regulation of MYOM2 and LILRA4 and down-regulation of MT-ATP8, CD83, and CCL3L1 was found in progressive disease group C. PCBP1, FOS, RGCC, S100B, G0S2, AREG, and LYN were highly expressed in favorable treatment response compared to unfavorable response. Our findings may offer a comprehensive understanding of the host immune profiles that influence a particular MAC-PD clinical course and could suggest an immunological mechanism associated with the disease progression of MAC-PD.
摘要:
鸟分枝杆菌复杂性肺病(MAC-PD)具有异质性的临床病程。然而,与MAC-PD临床病程相关的免疫谱有限.我们对21例MAC-PD患者的外周血单个核细胞进行单细胞RNA测序,分为三个临床疗程:A组,自发培养转化;B组,病情稳定,无抗生素治疗;C组,抗生素治疗的进行性疾病。与A组和B组相比,C组的NK细胞比例较低,单核细胞比例较高。而非经典单核细胞的比例下降。EGR1,HSPA1A,HSPA1B,与进行性疾病组C相比,自发性培养转化组A中CD83上调。在进行性疾病组C中发现MYOM2和LILRA4的上调和MT-ATP8,CD83和CCL3L1的下调。PCBP1,FOS,RGCC,S100B,G0S2,AREG,与不利反应相比,LYN在有利的治疗反应中高度表达。我们的发现可能提供对影响特定MAC-PD临床过程的宿主免疫谱的全面了解,并可能提示与MAC-PD疾病进展相关的免疫机制。
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