Impairment of T cell development and acute inflammatory response in HIV-1 Tat transgenic mice

Scientific Reports
Giuseppe FiumeIleana Quinto

Abstract

Immune activation and chronic inflammation are hallmark features of HIV infection causing T-cell depletion and cellular immune dysfunction in AIDS. Here, we addressed the issue whether HIV-1 Tat could affect T cell development and acute inflammatory response by generating a transgenic mouse expressing Tat in lymphoid tissue. Tat-Tg mice showed thymus atrophy and the maturation block from DN4 to DP thymic subpopulations, resulting in CD4(+) and CD8(+) T cells depletion in peripheral blood. In Tat-positive thymus, we observed the increased p65/NF-κB activity and deregulated expression of cytokines/chemokines and microRNA-181a-1, which are involved in T-lymphopoiesis. Upon LPS intraperitoneal injection, Tat-Tg mice developed an abnormal acute inflammatory response, which was characterized by enhanced lethality and production of inflammatory cytokines. Based on these findings, Tat-Tg mouse could represent an animal model for testing adjunctive therapies of HIV-1-associated inflammation and immune deregulation.

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Citations

Feb 26, 2016·Frontiers in Microbiology·Suhani Thakker, Subhash C Verma
Nov 10, 2016·International Journal of Molecular Sciences·Giuseppe FiumeIleana Quinto
Mar 24, 2017·Archivum Immunologiae Et Therapiae Experimentalis·Abdur Rahman Ansari, Huazhen Liu
Nov 16, 2018·International Journal of Molecular Sciences·Antonio PisanoGiuseppe Fiume
Mar 20, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Marilena PontorieroIleana Quinto
Feb 6, 2020·International Journal of Molecular Sciences·Eleonora VecchioIleana Quinto
Sep 12, 2019·Viruses·Francesco AlbanoGiuseppe Fiume
Dec 18, 2020·Frontiers in Pharmacology·Elisabetta CaiazzoCarla Cicala
Mar 16, 2021·Frontiers in Immunology·Tatsuya IshikawaTaishin Akiyama
Jun 12, 2021·Frontiers in Immunology·Mingli LuoXi Sun

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Datasets Mentioned

BETA
GSE65006

Methods Mentioned

BETA
transgenic
ELISA
lavage
lavages
dot blot
PCR
Electrophoretic Mobility Shift Assay
chip
flow cytometry
X-ray

Software Mentioned

ImageJ
Adobe Photoshop

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