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Immunoprofiling of fresh HAM/TSP blood samples shows altered innate cell responsiveness
- Source :
- PLoS Neglected Tropical Diseases, Vol 15, Iss 11, p e0009940 (2021), PLoS Neglected Tropical Diseases
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
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.<br />Author summary The infection by the Human T-cell Leukemia Virus-1 (HTLV-1) is quite frequent in Brazil. Between 1–5% of infected individuals develop a devastating neurodegenerative disease (HAM/TSP) as a result of a sustained inflammation in the central nervous system, with no effective treatment. So far, inflammation has been linked to the deregulated activation of T-cells, but the role of innate cells has not been investigated yet. In this work, we aimed to characterize the responsiveness of innate cells, as this immune population is cornerstone of efficient immune response, but also might participate in disease exacerbation found in chronic infection. Our findings suggest an impaired antiviral response and increased inflammatory responsiveness by dendritic cells and monocytes in HAM/TSP patients compared to asymptomatic carriers. This sustained inflammatory responsiveness upon innate cell activation could participate in the establishment of the HAM/TSP disease.
- Subjects :
- Male
RNA viruses
Physiology
Cell
RC955-962
Stimulation
NK cells
Pathology and Laboratory Medicine
Monocytes
Cohort Studies
Blood cell
White Blood Cells
Medical Conditions
Animal Cells
immune system diseases
Immune Physiology
hemic and lymphatic diseases
Arctic medicine. Tropical medicine
Tropical spastic paraparesis
Medicine and Health Sciences
Receptor
Immune Response
Human T-lymphotropic virus 1
Innate Immune System
T Cells
virus diseases
Middle Aged
Interleukin-12
Paraparesis, Tropical Spastic
Killer Cells, Natural
Leukemia
Infectious Diseases
medicine.anatomical_structure
Medical Microbiology
Viral Pathogens
Viruses
Cytokines
Female
Cellular Types
Pathogens
Public aspects of medicine
RA1-1270
Brazil
Research Article
Adult
endocrine system
Immune Cells
Inflammatory Diseases
Immunology
Antigen-Presenting Cells
Microbiology
Immune system
Retroviruses
medicine
Humans
Microbial Pathogens
Blood Cells
business.industry
Organisms
Public Health, Environmental and Occupational Health
Biology and Life Sciences
Dendritic Cells
Cell Biology
Htlv-1
Molecular Development
medicine.disease
Immunity, Innate
Immune System
business
Asymptomatic carrier
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 19352735 and 19352727
- Volume :
- 15
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- PLoS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....886b909f437b8959872deb69e7742a92