Apoptosis characterization in mononuclear blood leukocytes of HIV patients during dengue acute disease

Abstract

Dengue virus (DenV) co-circulation in Brazil represents a challenge for treatment and vaccine development. Despite public health impact, the occurrence of coinfections with other viruses is a common event. Increased T cell activation and altered inflammatory response are found during DENV coinfection with Human Immunodeficiency Virus (HIV) impacting HIV-pathogenesis. Even with Antiretroviral therapy (ARt), HiV-treated patients had chronic immune activation and lymphocyte apoptosis. However, apoptotic mechanisms have not been investigated during coinfection with DenV. our attention was attracted to apoptotic cell markers expressions in pBMcs from DenV and DenV/ HIV coinfected patients. We found CD4/CD8 ratio inversion in most coinfected patients. CD4 T and CD8 T-cell subsets from DENV and DENV/HIV groups expressed low levels of anti-apoptotic protein Bcl-2. Furthermore, CD8 CD95 double positive cells frequency expressing low levels of Bcl-2 were significantly higher in these patients. Additionally, the density of Bcl-2 on classical monocytes (CD14 ++ CD16 − ) was significantly lower during DENV infection. Upregulation of pro-apoptotic proteins and anti-apoptotic proteins were found in DenV and DenV/HiV, while catalase, an antioxidant protein, was upregulated mainly in DENV/HIV coinfection. These findings provide evidence of apoptosis triggering during DenV/HiV coinfection, which may contribute to knowledge of immunological response during DenV acute infection in HiV-patients treated with ARt.Dengue virus (DENV) and Human Immunodeficiency Virus (HIV) infections are currently a major public health concern in Brazil. Dengue is caused by any one of four DENV (1-4) serotypes spread by mosquitoes of aedes genus. DENV causes an acute febrile illness of a broad clinical spectrum presenting both asymptomatic and symptomatic forms that can evolve with severe and potentially fatal condition 1 . The hallmark of most serious clinical conditions is the vascular permeability increase that causes plasma leakage, leading to shock and death. Acquired Immunodeficiency Sydrome (AIDS) (is still considered an important cause of morbidity and mortality in the world. HIV infects CD4 T-cells, monocytes/macrophages and to a lesser extent in dendritic cells leading to progressive CD4 T-cell depletion and consequently pronounced immunosuppression in the absence of effective antiretroviral therapy (ART) 2 .Apoptosis, also called type I cell death, is a regulated process of cell death highly conserved among mammals and comprises a controlled self-destruction process to eliminate damaged, neoplastic and virus-infected cells 3 . Apoptosis program regulation is determined by interactions of three members of B-cell lymphoma-2 family proteins (Bcl-2): Bcl-2 homologous 3 (BH3)-only proteins, Bcl-2 proteins and Bcl-2 associated X protein (Bax)/Bcl-2 homologous antagonist/killer (Bak) effectors. It can be triggered by extrinsic [death receptors like p55 tumor necrosis factor TNF receptor-TNFRI, Fas/CD95, TRAIL/APO2-L (TNF-related apoptosis-inducing li...

Label‐Free Cell Viability Assay and Enrichment of Cryopreserved Cells Using Microfluidic Cytometry and On‐Demand Sorting

“…Apoptosis is a typical cause of death of primary PBMCs in patients with infectious disease, [49,50] resulting in low viability with a certain amount of apoptotic cells in cryopreserved primary PBMC samples. Thus, apoptotic PBMCs need to be discriminated from thawed primary PBMCs for accurate viability assays.…”

Avaliação dos aspectos clínicos, epidemiológicos e sorológicos da dengue em pacientes infectados pelo HIV: um estudo coorte prospectivo na cidade de Birigui, estado de São Paulo

“…Na coinfecção também é observada uma redução na relação CD4/CD8, causado por um aumento da porcentagem de CD8, porém as repercussões clínicas desta variação não estão claras. Também foi demonstrado uma queda significativa no número de linfócitos justificada por uma suprarregulação de proteínas com funções apoptóticas (TORRENTES-CARVALHO et al, 2020). Um aumento da expressão da proteína CCR5 em linfócitos T CD4+ e do CD107a (um marcador funcional de atividade de células NK) em ambos os tipos de linfócitos T também foi observado (TORRENTES-CARVALHO et al, 2016).…”