无症状HIV/利什曼原虫合并感染中的T细胞激活、衰老和耗竭

T-cell activation, senescence, and exhaustion in asymptomatic HIV/Leish co-infection.

作者信息

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

机构信息

Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, RN, Brazil.

Department of Infectious Disease, Health Science Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil.

出版信息

medRxiv. 2023 Mar 6:2023.03.06.23286828. doi: 10.1101/2023.03.06.23286828.

DOI:10.1101/2023.03.06.23286828

PMID:36945413

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10029033/

Abstract

BACKGROUND

is an opportunistic parasitic infection. An immunocompromised state increases the risk of converting asymptomatic infection to symptomatic visceral leishmaniasis (VL), which has a ~5% fatality rate even with treatment. HIV coinfection increases the risk of death from VL.

METHODS

A cross-sectional study was performed between 2014 and 2016 to determine the prevalence of infection in HIV positive subjects residing in the state of Rio Grande do Norte, Brazil (n=1,372) and of these a subgroup of subjects were followed longitudinally. Subsequent incident cases of VL were ascertained from a public health database through 2018. A subgroup (n=69) of the cross-sectional study subjects was chosen to assess immune status (T cell activation, senescence, exhaustion) and outcome. The data were compared between asymptomatic HIV+/+ (HIV/Leish), symptomatic visceral leishmaniasis (VL), recovered VL, DTH+ (Delayed-Type Hypersensitivity response - Leishmanin skin test), AIDS/VL, HIV+ only (HIV+), and Non-HIV/Non infection (control subjects).

RESULTS

The cross-sectional study showed 24.2% of HIV+ subjects had positive anti-IgG antibodies. After 3 years, 2.4% (8 of 333) of these HIV/Leish coinfected subjects developed AIDS/VL, whereas 1.05% (11 of 1,039) of HIV subjects with negative leishmania serology developed AIDS/VL. Poor adherence to antiretroviral therapy (p=0.0008) or prior opportunistic infections (p=0.0007) was associated with development of AIDS/VL. CD4+ (p=0.29) and CD8+ (p=0.38) T cells counts or viral load (p=0.34) were similar between asymptomatic HIV/Leish and HIV subjects. However, activated CD8CD38HLA-DR T cells were higher in asymptomatic HIV/Leish than HIV group. Likewise, senescent (CD57+) or exhausted (PD1) CD8 T cells were higher in asymptomatic HIV/Leish than in AIDS/VL or HIV groups.

CONCLUSION

Although asymptomatic HIV/Leish subjects had normal and similar CD4+ and CD8+ T cells counts, their CD8T cells had increased activation, senescence, and exhaustion, which could contribute to risk of developing VL.

摘要

背景

是一种机会性寄生虫感染。免疫功能低下状态会增加将无症状感染转变为有症状的内脏利什曼病（VL）的风险，即使经过治疗，其死亡率仍约为5%。合并感染HIV会增加因VL死亡的风险。

方法

在2014年至2016年期间进行了一项横断面研究，以确定居住在巴西北里奥格兰德州的HIV阳性受试者（n = 1372）中的感染患病率，其中一部分受试者进行了纵向随访。通过2018年的公共卫生数据库确定随后发生的VL病例。选择横断面研究受试者中的一个亚组（n = 69）来评估免疫状态（T细胞活化、衰老、耗竭）和结局。对无症状HIV+/+（HIV/利什曼病）、有症状的内脏利什曼病（VL）、康复的VL、DTH+（迟发型超敏反应 - 利什曼原虫皮肤试验）、AIDS/VL、仅HIV+（HIV+）以及非HIV/非感染（对照受试者）的数据进行了比较。

结果

横断面研究显示24.2%的HIV+受试者抗IgG抗体呈阳性。3年后，这些HIV/利什曼病合并感染受试者中有2.4%（333例中的8例）发展为AIDS/VL，而利什曼原虫血清学阴性的HIV受试者中有1.05%（1039例中的11例）发展为AIDS/VL。抗逆转录病毒治疗依从性差（p = 0.0008）或既往有机会性感染（p = 0.0007）与AIDS/VL的发生有关。无症状HIV/利什曼病组和HIV组之间的CD4+（p = 0.29）和CD8+（p = 0.38）T细胞计数或病毒载量（p = 0.34）相似。然而，无症状HIV/利什曼病组中活化的CD8CD38HLA-DR T细胞高于HIV组。同样，无症状HIV/利什曼病组中衰老的（CD57+）或耗竭的（PD1）CD8 T细胞高于AIDS/VL组或HIV组。