Ga(III) Nanoparticles Inhibit Growth of both Mycobacterium tuberculosis and HIV and Release of Interleukin-6 (IL-6) and IL-8 in Coinfected Macrophages.
Treatment of individuals coinfected with human immunodeficiency virus (HIV) type 1 andMycobacterium tuberculosisis challenging due to the prolonged treatment requirements, drug toxicity, and emergence of drug resistance. Mononuclear phagocytes (MP; macrophages) are one of the natural reservoirs for both HIV andM. tuberculosisHere, the treatment of HIV andM. tuberculosiscoinfection was studied by preloading human macrophages with MP-targeted gallium (Ga) nanoparticles to limit subsequent simultaneous infection with both HIV andM. tuberculosisGa nanoparticles provided sustained drug release for 15 days and significantly inhibited the replication of both HIV andM. tuberculosisAddition of Ga nanoparticles to MP already infected withM. tuberculosisor HIV resulted in a significant decrease in the magnitude of these infections, but the magnitude was less than that achieved with nanoparticle preloading of the MP. In addition, macrophages that were coinfected with HIV andM. tuberculosisand that were loaded with Ga nanoparticles reduced the levels of interleukin-6 (IL-6) and IL-8 secretion for up to 15 days after drug loading. Ga nanoparticles also reduced the levels of IL-6 and IL-8 secretion by ionomycin- and lipopolysaccharide-induced macrophages, likely by modulating the IκB kinase-β/NF-κB pathway. Delivery of Ga nanoparticles to macrophages is a potent long-acting approach for suppressing HIV andM. tuberculosiscoinfection of macrophagesin vitroand sets the stage for the development of new approaches to the treatment of these important infections.
Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Seoung-Ryoung
SR
Choi
Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.|Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.|Research Service, VA Medical Center Nebraska-Western Iowa, Omaha, Nebraska, USA.
Bradley E
BE
Britigan
Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA p.narayanasamy@unmc.edu.
Prabagaran
P
Narayanasamy
D002478:Cells, Cultured; D060085:Coinfection / Q000382:microbiology / Q000821:virology; D005708:Gallium / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008264:Macrophages / Q000382:microbiology / Q000821:virology; D053768:Metal Nanoparticles / Q000737:chemistry*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D005708:Gallium
IL-6; IL-8; Mycobacterium tuberculosis; human immunodeficiency virus; nanoparticle