Volume 12 Supplement 1

17th International Confernce on Human Retroviruses: HTLV and Related Viruses

Open Access

Monocyte accumulation is an early event in HAM/TSP pathogenesis, while monocyte activation and IFN-regulated gene expression persist in chronic HAM/TSP

  • Soraya Maria Menezes1,
  • Harry Freitag Muhammad1,
  • George Soares2,
  • Ricardo Khouri1, 2,
  • Daniele Decanine2,
  • Gilvaneia Silva Santos2,
  • Saul Velloso Schnitman2,
  • Ramon Kruschewsky3,
  • Giovanni López4,
  • Carolina Alvarez1, 4,
  • Michael Talledo4,
  • Eduardo Gotuzzo4, 5,
  • Bernardo Galvão-Castro3 and
  • Johan Van Weyenbergh1, 2Email author
Retrovirology201512(Suppl 1):O25

https://doi.org/10.1186/1742-4690-12-S1-O25

Published: 28 August 2015

Tattermusch et al (2012) identified an IFN-inducible gene signature in whole blood of HAM/TSP patients, with a strong myeloid component, while abortive HTLV-1 infection induces monocyte apoptosis (Sze et al. 2013). We previously demonstrated that B cell CD80 expression correlates to disease severity in HAM/TSP (Menezes et al 2014), whereas B cell CD86 is selectively up-regulated by IFN-beta in both HAM/TSP and multiple sclerosis (MS). In this study, we propose a cell type-and gene-specific, rather than a generalized IFN response in HAM/TSP. Using polychromatic flow cytometry, comprehensive phenotyping of monocytes (CD14, CD64, CD80, CD86, CD95/Fas, HLA-DR) was performed in a total of 53 individuals (HAM/TSP patients, asymptomatic HTLV-1-infected and uninfected controls), and absolute and relative monocyte counts were obtained from >600 HTLV-1-infected individuals with complete clinical follow-up and proviral load. Ex vivo monocyte levels increased in early HAM/TSP (p<0.01), independent of proviral load, and were significantly correlated to age of onset of HAM/TSP in both Brazilian and Peruvian cohorts. On the other hand, monocyte activation measured by systemic soluble CD14 was significantly increased in chronic (p<0.01) but not early HAM/TSP, whereas CD95 and CD86 expression in monocytes correlated negatively to disease progression. Interestingly, membrane expression of CD14 is down-regulated and CD95/CD86 up-regulated by IFN-beta in vitro (controls) and in vivo (MS), suggesting IFN-regulated expression of all three monocyte receptors in HAM/TSP. Transcriptomic analysis of whole blood vs. purified monocytes/B cells confirmed cell-specific expression of CD64/CD80/CD86 ex vivo, whereas a selective decrease of myeloid/monocyte-specific genes was observed upon in vitro culture of HAM/TSP PBMCs, possibly due to apoptosis of specific monocyte subsets. In conclusion, an increase in soluble CD14, as well as monocyte-specific expression of CD64, CD95 and CD86 differentially reflect disease progression in HAM/TSP, in addition to B-cell specific CD80 expression, arguing for a complex and compartmentalized IFN response.

Authors’ Affiliations

(1)
Rega Institute for Medical Research, Department of Microbiology and Immunology K.U
(2)
LIMI-CPqGM, Oswaldo Cruz Foundation (FIOCRUZ)
(3)
Bahiana School of Medicine and Public Health
(4)
Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia
(5)
Departamento de Medicina, Facultad de Medicina Alberto Hurtado, Universidad Peruana Cayetano Heredia

Copyright

© Menezes et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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