title: Minocycline attenuates HIV-1 infection and suppresses chronic immune activation in humanized NOD/LtsZ-scidIL-2Rγ(null) mice.
abstract: 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-2Rγ(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.
authors.affiliation: Immunology & Infectious Diseases, CHU de Liège - Université de Liège, GIGA I3, Liège, Belgium.
authors.forename: Maneesh
authors.initials: M
authors.lastname: Singh
authors.forename: Pratibha
authors.initials: P
authors.lastname: Singh
authors.forename: Dolores
authors.initials: D
authors.lastname: Vaira
authors.forename: Mathieu
authors.initials: M
authors.lastname: Amand
authors.forename: Souad
authors.initials: S
authors.lastname: Rahmouni
authors.forename: Michel
authors.initials: M
authors.lastname: Moutschen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008911:Minocycline / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; C556062:IL10 protein, mouse; D016753:Interleukin-10; D008911:Minocycline
keywords: HIV; humanized NOD/LtsZ-scidIL-2Rγnull mice; immune activation; minocycline