Article (Scientific journals)
Minocycline attenuates HIV-1 infection and suppresses chronic immune activation in humanized NOD/LtsZ-scidIL-2Rgamma(null) mice.
Singh, Maneesh; Singh, Pratibha; VAIRA, Dolorès et al.
2014In Immunology, 142 (4), p. 562-72
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Keywords :
Animals; Anti-Bacterial Agents/pharmacology; HIV Infections/drug therapy/genetics/immunology/pathology; HIV-1/physiology; Humans; Interleukin-10/genetics/immunology; Mice; Mice, Inbred NOD; Mice, SCID; Minocycline/pharmacology; Virus Replication/drug effects/immunology; HIV; humanized NOD/LtsZ-scidIL-2Rγnull mice; immune activation; minocycline
Abstract :
[en] More than a quarter of a century of research has established chronic immune activation and dysfunctional T cells as central features of chronic HIV infection and subsequent immunodeficiency. Consequently, the search for a new immunomodulatory therapy that could reduce immune activation and improve T-cell function has been increased. However, the lack of small animal models for in vivo HIV study has hampered progress. In the current study, we have investigated a model of cord blood haematopoietic progenitor cells (CB-HPCs) -transplanted humanized NOD/LtsZ-scidIL-2Rgamma(null) mice in which progression of HIV infection is associated with widespread chronic immune activation and inflammation. Indeed, HIV infection in humanized NSG mice caused up-regulation of several T-cell immune activation markers such as CD38, HLA-DR, CD69 and co-receptor CCR5. T-cell exhaustion markers PD-1 and CTLA-4 were found to be significantly up-regulated on T cells. Moreover, increased plasmatic levels of lipopolysaccharide, sCD14 and interleukin-10 were also observed in infected mice. Treatment with minocycline resulted in a significant decrease of expression of cellular and plasma immune activation markers, inhibition of HIV replication and improved T-cell counts in HIV-infected humanized NSG mice. The study demonstrates that minocycline could be an effective, low-cost adjunctive treatment to regulate chronic immune activation and replication of HIV.
Disciplines :
Immunology & infectious disease
Author, co-author :
Singh, Maneesh
Singh, Pratibha
VAIRA, Dolorès 
Amand, Mathieu ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Rahmouni, Souad  ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Moutschen, Michel  ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Language :
English
Title :
Minocycline attenuates HIV-1 infection and suppresses chronic immune activation in humanized NOD/LtsZ-scidIL-2Rgamma(null) mice.
Publication date :
2014
Journal title :
Immunology
ISSN :
0019-2805
eISSN :
1365-2567
Publisher :
Blackwell, Oxford, United Kingdom
Volume :
142
Issue :
4
Pages :
562-72
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) 2014 John Wiley & Sons Ltd.
Available on ORBi :
since 03 November 2014

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