T-cell activation and senescence in asymptomatic HIV/Leishmania infantum co-infection.

IF 3.4 2区医学 Q1 PARASITOLOGY

PLoS Neglected Tropical Diseases Pub Date : 2025-03-17 eCollection Date: 2025-03-01 DOI:10.1371/journal.pntd.0012848

Carolina de Oliveira Mendes-Aguiar, Manoella do Monte Alves, Amanda de Albuquerque Lopes Machado, Glória Regina de Góis Monteiro, Iara Marques Medeiros, Jose Wilton Queiroz, Iraci Duarte Lima, Eliardo G Costa, Richard D Pearson, Mary E Wilson, Marshall J Glesby, Eliana Lúcia Tomaz do Nascimento, Selma Maria Bezerra Jerônimo

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Abstract

Background: Leishmania infantum can be an opportunistic pathogen, with an immunocompromised status increasing the risk of converting asymptomatic infection to symptomatic visceral leishmaniasis (VL). VL has approximately 5% fatality rate; and HIV coinfection (AIDS/VL) increases this risk. We hypothesized that, relative to those with HIV alone, people with co-infection would have altered T cell activation which could impact on the risk of VL.

Methods: A cross-sectional study was performed between 2014 and 2016 to determine the prevalence of L. infantum infection in people living with HIV (PLHIV) residing in Brazil (n = 1,372). Subsequent incident cases of VL were ascertained from a public health database through 2018 and from a cohort of families with VL. Immune status of 69 participants was evaluated and comparisons made between those with and without HIV, with latent or with active Leishmania infection and those without HIV but with active or resolved Leishmania or T cell hypersensitivity to Leishmania antigen and healthy control subjects.

Results: A total of 24.2% of PLHIV had positive anti-IgG L. infantum antibodies. The relative risk of developing AIDS/VL was 2.27 (95% CI: 0.920 to 5.59; p = 0.07) to HIV/Leish coinfected subjects with positive leishmania serology compared to HIV subjects without leishmania serology. Poor adherence to antiretroviral therapy (p = 0.0008) or prior opportunistic infections (p = 0.0007) was associated with development of AIDS/VL in asymptomatic HIV/Leish. CD4+ and CD8+ T cells counts or viral load were similar between asymptomatic HIV/Leish and HIV subjects. However, activated CD8+CD38+HLA-DR+ T cells were higher in asymptomatic HIV/Leish than HIV. Likewise, senescent (CD57+) and PD1+ CD8+ T cells were higher in asymptomatic HIV/Leish than in AIDS/VL or HIV groups.

Conclusion: Although asymptomatic HIV/Leish subjects had CD4+ and CD8+ T cells similar to HIV alone, their CD8+T cells had increased activation and senescence which could contribute to risk of developing VL.

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无症状HIV/利什曼原虫合并感染的t细胞活化和衰老。

背景：婴儿利什曼原虫可能是一种机会性病原体，免疫力低下会增加无症状感染转变为有症状的内脏利什曼病（VL）的风险。内脏利什曼病的致死率约为 5%，而艾滋病病毒合并感染（艾滋病/内脏利什曼病）会增加这种风险。我们假设，与单独感染艾滋病病毒者相比，合并感染者的T细胞活化会发生改变，这可能会影响VL的风险：我们在 2014 年至 2016 年间开展了一项横断面研究，以确定居住在巴西的艾滋病病毒感染者（PLHIV）（n = 1,372）的婴儿嗜血杆菌感染率。随后的VL事件病例是从公共卫生数据库（截至2018年）和VL患者家庭队列中确定的。对 69 名参与者的免疫状况进行了评估，并对感染艾滋病毒和未感染艾滋病毒者、利什曼原虫潜伏感染者或活动感染者、未感染艾滋病毒但利什曼原虫活动或缓解或对利什曼原虫抗原 T 细胞过敏者以及健康对照组进行了比较：共有 24.2% 的 PLHIV 患者的抗 IgG 幼年利什曼病抗体呈阳性。与没有利什曼病血清学检测结果的艾滋病毒感染者相比，利什曼病血清学检测结果呈阳性的艾滋病毒/利什曼病合并感染者患艾滋病/VL的相对风险为2.27（95% CI：0.920-5.59；p = 0.07）。抗逆转录病毒治疗依从性差（p = 0.0008）或既往机会性感染（p = 0.0007）与无症状 HIV/Leish 感染者的 AIDS/VL 发展相关。无症状 HIV/Leish 感染者与 HIV 感染者的 CD4+ 和 CD8+ T 细胞计数或病毒载量相似。然而，无症状 HIV/Leish 中活化的 CD8+CD38+HLA-DR+ T 细胞高于 HIV。同样，无症状 HIV/Leish 中衰老（CD57+）和 PD1+ CD8+ T 细胞也高于 AIDS/VL 或 HIV 组：结论：虽然无症状 HIV/Leish 受试者的 CD4+ 和 CD8+ T 细胞与单独感染 HIV 者相似，但他们的 CD8+ T 细胞的活化和衰老程度增加，这可能会增加罹患 VL 的风险。

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PLoS Neglected Tropical Diseases PARASITOLOGY-TROPICAL MEDICINE

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723

期刊介绍： PLOS Neglected Tropical Diseases publishes research devoted to the pathology, epidemiology, prevention, treatment and control of the neglected tropical diseases (NTDs), as well as relevant public policy. The NTDs are defined as a group of poverty-promoting chronic infectious diseases, which primarily occur in rural areas and poor urban areas of low-income and middle-income countries. Their impact on child health and development, pregnancy, and worker productivity, as well as their stigmatizing features limit economic stability. All aspects of these diseases are considered, including: Pathogenesis Clinical features Pharmacology and treatment Diagnosis Epidemiology Vector biology Vaccinology and prevention Demographic, ecological and social determinants Public health and policy aspects (including cost-effectiveness analyses).