IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques.

Autor: Ortiz AM; Program in Tissue Immunity and Repair and Immunopathogenesis Section, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA., Klase ZA; Program in Tissue Immunity and Repair and Immunopathogenesis Section, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA.; Department of Biological Sciences, University of the Sciences, Philadelphia, Pennsylvania, USA., DiNapoli SR; Program in Tissue Immunity and Repair and Immunopathogenesis Section, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA., Vujkovic-Cvijin I; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California, USA., Carmack K; Program in Tissue Immunity and Repair and Immunopathogenesis Section, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA., Perkins MR; Program in Tissue Immunity and Repair and Immunopathogenesis Section, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA., Calantone N; Program in Tissue Immunity and Repair and Immunopathogenesis Section, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA., Vinton CL; Program in Tissue Immunity and Repair and Immunopathogenesis Section, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA., Riddick NE; Program in Tissue Immunity and Repair and Immunopathogenesis Section, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA., Gallagher J; Program in Tissue Immunity and Repair and Immunopathogenesis Section, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA., Klatt NR; Program in Tissue Immunity and Repair and Immunopathogenesis Section, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA.; Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle, Washington, USA., McCune JM; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California, USA., Estes JD; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, USA., Paiardini M; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA., Brenchley JM; Program in Tissue Immunity and Repair and Immunopathogenesis Section, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA.
Jazyk: angličtina
Zdroj: Mucosal immunology [Mucosal Immunol] 2016 Mar; Vol. 9 (2), pp. 458-67. Date of Electronic Publication: 2015 Aug 19.
DOI: 10.1038/mi.2015.75
Abstrakt: Increased mortality in antiretroviral (ARV)-treated, HIV-infected individuals has been attributed to persistent immune dysfunction, in part due to abnormalities at the gastrointestinal barrier. In particular, the poor reconstitution of gastrointestinal Th17 cells correlates with residual translocation of dysbiotic, immunostimulatory microflora across a compromised intestinal epithelial barrier. We have previously demonstrated that oral probiotics promote increased intestinal CD4(+) T-cell reconstitution during ARV treatment in a non-human primate model of HIV infection; however, essential mucosal T-cell subsets, such as Th17 cells, had limited recovery. Here, we sought to promote Th17 cell recovery by administering interleukin (IL)-21 to a limited number of ARV-treated, probiotic-supplemented, Simian Immunodeficiency Virus (SIV)-infected pigtailed macaques. We demonstrate that probiotic and IL-21 supplementation of ARVs are associated with enhanced polyfunctional Th17 expansion and reduced markers of microbial translocation and dysbiosis as compared with infected controls receiving ARVs alone. Importantly, treatment resulted in fewer morbidities compared with controls, and was independent of increased immune activation or loss of viral suppression. We propose that combining ARVs with therapeutics aimed at restoring intestinal stasis may significantly improve disease prognosis of ARV-treated, HIV-infected individuals.
Databáze: MEDLINE
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