Immunoprofiling of fresh HAM/TSP blood samples shows altered innate cell responsiveness.

Brenda Rocamonde,Augusto Cesar Penalva De Oliveira,Nicolas Futsch,Omran Allatif,Renaud Mahieux,Jorge Casseb,Noemia Orii,Hélène Dutartre,Masao Matsuoka

doi:10.1371/journal.pntd.0009940

Abstract

The Human T-cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a devastating neurodegenerative disease with no effective treatment, which affects an increasing number of people in Brazil. Immune cells from the adaptive compartment are involved in disease manifestation but whether innate cell functions participate in disease occurrence has not been evaluated. In this study, we analyzed innate cell responses at steady state and after blood cell stimulation using an agonist of the toll-like receptor (TLR)7/8-signaling pathway in blood samples from HTLV-1-infected volunteers, including asymptomatic carriers and HAM/TSP patients. We observed a lower response of IFNα+ DCs and monocytes in HAM/TSP compared to asymptomatic carriers, as a potential consequence of corticosteroid treatments. In contrast, a higher frequency of monocytes producing MIP-1α and pDC producing IL-12 was detected in HAM/TSP blood samples, together with higher IFNγ responsiveness of NK cells, suggesting an increased sensitivity to inflammatory response in HAM/TSP patients compared to asymptomatic carriers. This sustained inflammatory responsiveness could be linked or be at the origin of the neuroinflammatory status in HAM/TSP patients. Therefore, the mechanism underlying this dysregulations could shed light onto the origins of HAM/TSP disease.

Highlights

The Human T-cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) [1,2] is a progressive neurodegenerative disease characterized by the demyelination of the middle-to-lower thoracic cord [1], with a high prevalence in Brazil [3]
Sociodemographic factors, proviral load (PVL) or innate cell frequencies are similar in asymptomatic carriers (AC) and HAM/TSP
An increased PVL was considered the only hallmark of HAM/ TSP [22], we found no significance differences between AC and HAM/TSP subjects (Fig 1A)

Summary

Introduction

The Human T-cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) [1,2] is a progressive neurodegenerative disease characterized by the demyelination of the middle-to-lower thoracic cord [1], with a high prevalence in Brazil [3]. Viral and immune characterization of HAM/ TSP patients identify some markers of pathogenicity, such as an increased proviral load (PVL, i.e. the number of integrated copies of the viral genome in the host cells) or higher frequency of CD8+ T-cells and higher secretion of pro-inflammatory cytokines such as TNFα and IFNγ [4] Those markers do not allow to anticipate the development of HAM/TSP in infected asymptomatic carriers, since some of them present an elevated PVL without developing any myelopathy, and alterations in T-cell frequencies and cytokine secretion is only detectable in patients with disease manifestations, and not in infected asymptomatic carriers [5]. The identification of immune markers predicting the disease progression is required

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