Hydroxyl functionalized multi-walled carbon nanotubes modulate immune responses without increasing 2009 pandemic influenza A/H1N1 virus titers in infected mice
Autor: | Julia C. Loeb, Hao Chen, L. Cody Smith, William L. Castleman, Sara T. Humes, Indu Venu Sabaraya, Melanie J. Rose, John A. Lednicky, Navid B. Saleh, Sarah E. Robinson, Tara Sabo-Attwood |
---|---|
Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Chemokine medicine.medical_treatment Inflammation Toxicology Virus Microbiology Mice 03 medical and health sciences Influenza A Virus H1N1 Subtype 0302 clinical medicine Immune system Orthomyxoviridae Infections medicine Animals Pharmacology medicine.diagnostic_test biology Nanotubes Carbon Chemistry Lung Injury Mice Inbred C57BL 030104 developmental biology Cytokine Bronchoalveolar lavage Gene Expression Regulation 030220 oncology & carcinogenesis TLR3 biology.protein Tumor necrosis factor alpha medicine.symptom |
Zdroj: | Toxicology and Applied Pharmacology. 404:115167 |
ISSN: | 0041-008X |
Popis: | Growing use of carbon nanotubes (CNTs) have garnered concerns regarding their association with adverse health effects. Few studies have probed how CNTs affect a host's susceptibility to pathogens, particularly respiratory viruses. We reported that exposure of lung cells and mice to pristine single-walled CNTs (SWCNTs) leads to significantly increased influenza virus H1N1 strain A/Mexico/4108/2009 (IAV) titers in concert with repressed antiviral immune responses. In the present study, we investigated if hydroxylated multi-walled CNTs (MWCNTs), would result in similar outcomes. C57BL/6 mice were exposed to 20 μg MWCNTs on day 0 and IAV on day 3 and samples were collected on day 7. We investigated pathological changes, viral titers, immune-related gene expression in lung tissue, and quantified differential cell counts and cytokine and chemokine levels in bronchoalveolar lavage fluid. MWCNTs alone caused mild inflammation with no apparent changes in immune markers whereas IAV alone presented typical infection-associated inflammation, pathology, and titers. The co-exposure (MWCNTs + IAV) did not alter titers or immune cell profiles compared to the IAV only but increased concentrations of IL-1β, TNFα, GM-CSF, KC, MIPs, and RANTES and inhibited mRNA expression of Tlr3, Rig-i, Mda5, and Ifit2. Our findings suggest MWCNTs modulate immune responses to IAV with no effect on the viral titer and modest pulmonary injury, a result different from those reported for SWCNT exposures. This is the first study to show that MWCNTs modify cytokine and chemokine responses that control aspects of host defenses which may play a greater role in mitigating IAV infections. |
Databáze: | OpenAIRE |
Externí odkaz: |