Association of Human T Lymphotropic Virus 1 Amplification of Periodontitis Severity with Altered Cytokine Expression in Response to a Standard Periodontopathogen Infection

Garlet, Gustavo; Giozza, Silvana Pereira; Silveira, Elcia Maria; Claudino, Marcela; Santos, Sara; Avila-Campos, Mario Júlio; Martins, Wilson; Cardoso, Cristina Ribeiro de Barros; Trombone, Ana Paula; Campanelli, Ana Paula; Carvalho, Edgar M.; Silva, Joaeo Santana

doi:10.1086/649871

Cited by 37 publications

(38 citation statements)

References 44 publications

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“…IL-12 secretion by neutrophils was found to be elevated in asymptomatic and symptomatic HTLV-1 carriers[43]. IL-12 was also found to be elevated in HTLV-1 patients with periodontitis compared with patients with periodontitis only[44] and in HTLV-1 patients with HAM/TSP compared to uninfected patients with neurological diseases[45]. A type I interferon-induced gene signature has been identified in individuals with HAM/TSP but abnormal plasma levels of type I or type II IFNs haven’t been detected in those patients, probably because of the short half-lives of IFNs[46].…”

Section: Discussionmentioning

confidence: 99%

MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications

et al. 2017

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HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb) infection, suggesting that immunological defect are associated with HTLV-1 infection. Evidence suggests an important role for Mucosal-associated invariant T (MAIT) cells in the early control of Mtb infection. Chronic viral infections like HIV and HCV have been associated with decreased frequency and functionality of MAIT cells. We hypothesized that HTLV-1 infection is associated with similar perturbations in MAIT cells. We investigated MAIT cell frequency, phenotype, and function by flow cytometry in a cohort of 10 asymptomatic and 10 HAM/TSP HTLV-1 infected patients. We found that MAIT cells from HTLV-1-infected subjects were reduced and showed high co-expression of the activation markers CD38 and HLA-DR but normal levels of CCR6 and CD127. MAIT cells had a lower expression of the transcription factor PLZF in HAM/TSP patients. Unlike Tax-specific CD8+T cells, which are hyperfunctional, MAIT cells from HTLV-1-infected subjects had a poor IFNγ response following antigen stimulation. MAIT cell perturbations in HTLV-1 infection were not associated with HTLV-1 proviral load and MAIT cells were not infected by HTLV-1 in vivo. Rather, MAIT cells loss was associated with immune activation. Overall, our results do not support a role for MAIT cells in HAM/TSP pathogenesis but reduced numbers of MAIT cells, together with their poor functionality, could contribute to the increased susceptibility of HTLV-1-infected individuals to other infectious agents.

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Section: Discussionmentioning

confidence: 99%

MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications

et al. 2017

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“…These mechanisms have been documented not only in HAM/TSP, but also in other diseases associated with HTLV-1 infection, including infective dermatitis,34 periodontal disease,27 HTLV-1-associated arthropathy,35 sicca syndrome,16 and isolated neurologic deficits 36. These findings clearly implicate HTLV-1 infection as central to the observed clinical pathology.…”

Section: Discussionmentioning

confidence: 79%

“…Over the last ten years, evidence has accumulated that, in addition to HAM/TSP and ATLL, HTLV-1 infection is capable of causing a variety of diseases including uveitis,9-11 periodontal disease,23, 27 sicca syndrome,16 HTLV-1 associated arthropathy,14, 15 and a large number of neurologic deficits 17-22. It is particularly striking that these findings occur in a large group of individuals traditionally considered to be asymptomatic HTLV-1 carriers, indicating that morbidity associated with HTLV-1 is much higher than has been previously considered 19, 28-31.…”

Section: Discussionmentioning

confidence: 99%

Clinical manifestations in individuals with recent diagnosis of HTLV type I infection

Poetker¹,

Porto²,

Giozza³

et al. 2011

Journal of Clinical Virology

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“…Little is known about IL-17 production in HTLV-1 infection. It has been reported that expression of IL-17 mRNA is induced by Tax in HTLV-1 infected T-cell lines [43] and increased in periodontal tissue of HTLV-1-infected subjects with periodontitis [71]. However, IL-17 production from a specific CD4 + T-cell subset is reduced among HAM/TSP patients [44].…”

Section: Resultsmentioning

confidence: 99%

Expansion in CD39+ CD4+ Immunoregulatory T Cells and Rarity of Th17 Cells in HTLV-1 Infected Patients Is Associated with Neurological Complications

et al. 2013

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HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develops HAM/TSP. CD4+ T cells are the main target of infection and play a pivotal role in regulating immunity to HTLV and are hypothesized to participate in the pathogenesis of HAM/TSP. The CD39 ectonucleotidase receptor is expressed on CD4+ T cells and based on co-expression with CD25, marks T cells with distinct regulatory (CD39+CD25+) and effector (CD39+CD25−) function. Here, we investigated the expression of CD39 on CD4+ T cells from a cohort of HAM/TSP patients, HTLV-1 asymptomatic carriers (AC), and matched uninfected controls. The frequency of CD39+ CD4+ T cells was increased in HTLV-1 infected patients, regardless of clinical status. More importantly, the proportion of the immunostimulatory CD39+CD25− CD4+ T-cell subset was significantly elevated in HAM/TSP patients as compared to AC and phenotypically had lower levels of the immunoinhibitory receptor, PD-1. We saw no difference in the frequency of CD39+CD25+ regulatory (Treg) cells between AC and HAM/TSP patients. However, these cells transition from being anergic to displaying a polyfunctional cytokine response following HTLV-1 infection. CD39−CD25+ T cell subsets predominantly secreted the inflammatory cytokine IL-17. We found that HAM/TSP patients had significantly fewer numbers of IL-17 secreting CD4+ T cells compared to uninfected controls. Taken together, we show that the expression of CD39 is upregulated on CD4+ T cells HAM/TSP patients. This upregulation may play a role in the development of the proinflammatory milieu through pathways both distinct and separate among the different CD39 T cell subsets. CD39 upregulation may therefore serve as a surrogate diagnostic marker of progression and could potentially be a target for interventions to reduce the development of HAM/TSP.

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Association of Human T Lymphotropic Virus 1 Amplification of Periodontitis Severity with Altered Cytokine Expression in Response to a Standard Periodontopathogen Infection

Abstract: HTLV-1 may play a critical role in the pathogenesis of periodontal disease through the deregulation of the local cytokine network, resulting in an exacerbated response against a standard periodontopathogen infection.

Cited by 37 publications

References 44 publications

MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications

MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications

Clinical manifestations in individuals with recent diagnosis of HTLV type I infection

Expansion in CD39+ CD4+ Immunoregulatory T Cells and Rarity of Th17 Cells in HTLV-1 Infected Patients Is Associated with Neurological Complications

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