Minocycline attenuates HIV-1 infection and suppresses chronic immune activation in humanized NOD/LtsZ-scidIL-2Rgamma(null) mice.

Singh, Maneesh; Singh, Pratibha; VAIRA, Dolorès; Amand, Mathieu; Rahmouni, Souad; Moutschen, Michel

doi:10.1111/imm.12246

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.

2014 • In Immunology, 142 (4), p. 562-72

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https://hdl.handle.net/2268/173515

DOI
10.1111/imm.12246

PubMed
24409837

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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 :

Pages :

562-72

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 03 November 2014

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