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Host-directed therapies that augment host immune effector mechanisms may serve as important adjunctive therapies for tuberculosis treatment. We evaluated the activity of denileukin diftitox in an acute mouse model of tuberculosis (TB) infection and analyzed the cellular composition and bacterial burden in lungs and spleens. These in vivo studies show that denileukin diftitox potentiates standard TB treatment in the mouse model, an effect which may be due to depletion of T-regulatory and myeloid-derived suppressor cells during TB infection. Our results indicate that denileukin diftitox and other suppressor cell-depleting therapies may be useful adjunctive, host-directed therapies for TB. [ABSTRACT FROM AUTHOR]

Background: Sensitive assays are needed for detection of residual human immunodeficiency virus (HIV) in patients with undetectable plasma viral loads to determine whether eradication strategies are effective. The gold standard quantitative viral outgrowth assay (QVOA) underestimates the magnitude of the viral reservoir. We sought to determine whether xenograft of leukocytes from HIV type 1 (HIV)-infected patients with undetectable plasma viral loads into immunocompromised mice would result in viral amplification.Methods: Peripheral blood mononuclear cells or purified CD4(+) T cells from HIV or simian immunodeficiency virus (SIV)-infected subjects with undetectable plasma viral loads were adoptively transferred into NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) mice. The mice were monitored for viremia following depletion of human CD8(+) T cells to minimize antiviral activity. In some cases, humanized mice were also treated with activating anti-CD3 antibody.Results: With this murine viral outgrowth assay (MVOA), we successfully amplified replication-competent HIV or SIV from all subjects tested, including 5 HIV-positive patients receiving suppressive antiretroviral therapy (ART) and 6 elite controllers or suppressors who were maintaining undetectable viral loads without ART, including an elite suppressor from whom we were unable to recover virus by QVOA.Conclusions: Our results suggest that the MVOA has the potential to serve as a powerful tool to identify residual HIV in patients with undetectable viral loads. [ABSTRACT FROM AUTHOR]