High IFN-&amp;#947;/IL-10 Expression Ratio and Increased Frequency of Persistent Human T-Cell Lymphotropic Virus Type 1-Infected Clones Are Associated with Human T-Cell Lymphotropic Virus Type 1-Associated Myelopathy/Tropical Spastic Paraparesis Development

Espíndola, Otávio de Melo; Oliveira, Luã C; Ferreira, Priscilla M S; Leite, Ana Cláudia Celestino Bezerra; Lima, Marco Antônio; Andrada-Serpa, Maria José

doi:10.1159/000371766

Cited by 19 publications

(19 citation statements)

References 36 publications

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“…Dysregulation of the immune cytokine networks in the HAM/TSP and ATLL patients, is characterized by an exacerbated expression of the pro-inflammatory or immunosuppressive cytokines, respectively, which have detrimental effects on overall immune responses. In addition to the elevated levels of these cytokines in the fluids of patients, it is more likely that direct dysregulations of the balance between functionally opposite cytokines, such as IFN-γ/IL-10 balance, contributes to the pathogenesis [96,149]. A complex network of cytokines could first generate a microenvironment, advantageous to the persistence of the HTLV-1-infected cells and, then, could contribute to the HTLV-1-induced diseases development.…”

Section: Discussionmentioning

confidence: 99%

Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases

Futsch

Prates

Mahieux

et al. 2018

Viruses

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Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of a neural chronic inflammation, called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and of a malignant lymphoproliferation, called the adult T-cell leukemia/lymphoma (ATLL). The mechanisms through which the HTLV-1 induces these diseases are still unclear, but they might rely on immune alterations. HAM/TSP is associated with an impaired production of pro-inflammatory cytokines and chemokines, such as IFN-γ, TNF-α, CXCL9, or CXCL10. ATLL is associated with high levels of IL-10 and TGF-β. These immunosuppressive cytokines could promote a protumoral micro-environment. Moreover, HTLV-1 infection impairs the IFN-I production and signaling, and favors the IL-2, IL-4, and IL-6 expression. This contributes both to immune escape and to infected cells proliferation. Here, we review the landscape of cytokine dysregulations induced by HTLV-1 infection and the role of these cytokines in the HTLV-1-associated diseases progression.

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Section: Discussionmentioning

confidence: 99%

Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases

Futsch

Prates

Mahieux

et al. 2018

Viruses

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“…HTLV‐1 is a persistent infection, with 2–5% of infected individuals going on to contract two main diseases: ATLL and HAM/TSP [Espíndola et al, ]. Accordingly, most HTLV‐1‐infected individuals remain asymptomatic carriers [Silva et al, ].…”

Section: Discussionmentioning

confidence: 99%

“…The host's immune response against HTLV‐1‐infected T‐cells is induced by CTLs in the central nervous system, resulting in the production of Th1 cytokines such as IFN γ, IL‐2, and TNF‐α by activated cells, which leads to the destruction of neurons [Espíndola et al, ]. Expression of pro‐inflammatory IFN γ is intensified in HAM/TSP patients and ACs compared to healthy people [Menezes et al, ].…”

Section: Discussionmentioning

confidence: 99%

“…Since the proliferation of viruses is cell‐dependent, it follows that proviral load (PVL) is defined as a number of peripheral blood mononuclear cells (PBMCs) that contain the integrated provirus [Arnold et al, ]. PVL with a high HTLV‐1 content can be used as a suitable indicator for neurological involvement [Espíndola et al, ], and is also an effective biological marker for understanding the pathology of HTLV‐1 [Hekmat et al, ].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of HTLV‐1 HBZ and proviral load, together with host IFN λ3, in pathogenesis of HAM/TSP

Mozhgani

Jaberi

Rezaee

et al. 2016

Journal of Medical Virology

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Human T-cell lymphotropic virus 1 (HTLV-1) is associated with two progressive diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Although HTLV-1 proviral load (PVL) has been introduced as a risk factor for these diseases' progression, it is not sufficient on its own to yield an accurate estimation of the outcome of the infection. In the present study, PVL and HTLV-1 basic leucine zipper factor (HBZ) expression level as viral factors, and IFN λ3 as a host factor, were evaluated in HAM/TSP patients and HTLV-1 asymptomatic carriers (ACs). During 2014-2015, 12 HAM/TSP patients and 18 ACs who had been referred to the HTLV-1 Clinic, Ghaem Hospital, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran, were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated and the DNA and mRNA were extracted for quantification of HBZ, IFN λ3 expression, and PVL using real-time PCR (TaqMan method). Although the PVL was higher in the HAM/TSP group, with a 94% confidence interval, there were no considerable differences in terms of HBZ mRNA and PVL between ACs and HAM patients. IFN λ3 expression in the HAM/TSP group was significantly higher than in the ACs (P = 0.02). To the best of our knowledge, no study has evaluated the expression level of IFN λ3 in HTLV-1 positive patients. The immune response against HTLV-1 viral antigens and virulent factors will therefore further refine our knowledge of interactions between the virus and host in the pathogenesis of HTLV-1-related disorders. The virus PVL and the host IFN λ3 can be used as pathogenic factors of HTLV-1 infected patients at risk of HAM/TSP manifestation. J. Med. Virol. 89:1102-1107, 2017. © 2016 Wiley Periodicals, Inc.

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“…These were IL-4/IFN-␥ (indicator of Th2/Th1 balance) and IL-4/TNF-␣ (indicator of Th2 response/proinflammatory innate immune response). This approach has been extensively used in previous studies to determine the balance between anti-inflammatory and proinflammatory responses triggered by different stimuli (47)(48)(49). IL-4 was primarily considered as anti-inflammatory cytokine instead of IL-10 since IL-10 production is under the control of IL-4 (50-52).…”

Section: Methodsmentioning

confidence: 99%

Depletion of Blautia Species in the Microbiota of Obese Children Relates to Intestinal Inflammation and Metabolic Phenotype Worsening

et al. 2020

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Cross-sectional studies conducted with obese and control subjects have suggested associations between gut microbiota alterations and obesity, but the links with specific disease phenotypes and proofs of causality are still scarce. The present study aimed to profile the gut microbiota of lean and obese children with and without insulin resistance to characterize associations with specific obesity-related complications and understand the role played in metabolic inflammation. Through massive sequencing of 16S rRNA gene amplicons and data analysis using a novel permutation approach, we have detected decreased incidence of Blautia species, especially Blautia luti and B. wexlerae, in the gut microbiota of obese children, which was even more pronounced in cases with both obesity and insulin resistance. There was also a parallel increase in proinflammatory cytokines and chemokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and monocyte chemoattractant protein 1 [MCP-1]) in feces of obese children compared to those of lean ones. B. luti and B. wexlerae were also shown to exert an anti-inflammatory effect in peripheral blood mononuclear cell cultures in vitro, compared to non-obesity-associated species. We suggest that the depletion of B. luti and B. wexlerae species in the gut ecosystem may occur in cases of obesity and contribute to metabolic inflammation leading to insulin resistance. IMPORTANCE Child obesity constitutes a risk factor for developing insulin resistance which, if sustained, could lead to more severe conditions like type 2 diabetes (T2D) in adulthood. Our study identified previously unknown species whose depletion (Blautia luti and Blautia wexlerae) is associated with insulin resistance in obese individuals. Our results also indicate that these bacterial species might help to reduce inflammation causally linked to obesity-related complications. Childhood is considered a window of opportunity to tackle obesity. These new findings provide, therefore, valuable information for the future design of microbiota-based strategies for the early prevention of obesity-related complications.

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High IFN-γ/IL-10 Expression Ratio and Increased Frequency of Persistent Human T-Cell Lymphotropic Virus Type 1-Infected Clones Are Associated with Human T-Cell Lymphotropic Virus Type 1-Associated Myelopathy/Tropical Spastic Paraparesis Development

Cited by 19 publications

References 36 publications

Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases

Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases

Evaluation of HTLV‐1 HBZ and proviral load, together with host IFN λ3, in pathogenesis of HAM/TSP

Depletion of Blautia Species in the Microbiota of Obese Children Relates to Intestinal Inflammation and Metabolic Phenotype Worsening

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