Mthembu Maphe, Claassen Helgard, Khuzwayo Sharon, Voillet Valentin, Naidoo Anneta, Spillner Jule S, Nyamande Kennedy, Khan Dilshaad Fakey, Maharaj Priya, Mitha Mohammed, Mhlane Zoey, Karim Farina, Andersen-Nissen Erica, Ndung'u Thumbi, Pollara Gabriele, Wong Emily B
Africa Health Research Institute, Durban, South Africa.
University of KwaZulu-Natal, Medical School, Durban, South Africa.
iScience. 2024 Oct 16;27(11):111137. doi: 10.1016/j.isci.2024.111137. eCollection 2024 Nov 15.
HIV causes susceptibility to respiratory pathogens, including tuberculosis (TB), but the underlying immunological mechanisms remain incompletely understood. We obtained whole blood and bronchoalveolar lavage (BAL) from TB-exposed people in the presence or absence of antiretroviral-naïve HIV co-infection. Bulk transcriptional profiling demonstrated compartment-specific enrichment of immunological processes. Systems-level deconvolution of whole blood from people living with HIV identified elevated type I and type II interferon cytokine activity and T cell proliferation. Transcriptional modules derived from both peripheral blood and sorted BAL immune cells demonstrated an increased frequency of effector memory CD8 T cells in whole BAL samples. Both compartments displayed reduced induction of CD8 T-cell-derived interleukin-17A (IL-17A) in people with HIV, associated with elevated T cell regulatory molecule expression. The data suggest that dysfunctional CD8 T cell responses in uncontrolled HIV may contribute to compromised respiratory immunity to pathogens, a process that could be modulated by host-directed therapies that target CD8 T cell effector functions.
人类免疫缺陷病毒（HIV）会使人易感染呼吸道病原体，包括结核病（TB），但其潜在的免疫机制仍未完全明确。我们从接触过结核病的人群中获取全血和支气管肺泡灌洗（BAL）样本，这些人群存在或不存在未接受过抗逆转录病毒治疗的HIV合并感染情况。大量转录谱分析显示了免疫过程在不同区室的特异性富集。对HIV感染者的全血进行系统水平的反卷积分析，发现I型和II型干扰素细胞因子活性以及T细胞增殖升高。从外周血和分选的BAL免疫细胞中获得的转录模块显示，全BAL样本中效应记忆CD8 T细胞的频率增加。在HIV感染者中，两个区室的CD8 T细胞衍生的白细胞介素-17A（IL-17A）诱导均减少，这与T细胞调节分子表达升高有关。数据表明，未得到控制的HIV感染中功能失调的CD8 T细胞反应可能导致对病原体的呼吸道免疫受损，这一过程可能通过针对CD8 T细胞效应功能的宿主导向疗法进行调节。
