Characterization of immune responses of human PBMCs infected with Mycobacterium tuberculosis H37Ra: Impact of donor declared BCG vaccination history on immune responses and M. tuberculosis growth.
Sudha BhavanamGina R RayatMonika KeelanDennis KunimotoSteven J DrewsPublished in: PloS one (2018)
This study characterized the immune responses in early Mycobacterium tuberculosis (Mtb) H37Ra infection of human peripheral blood mononuclear cell (PBMC)-collagen matrix culture and the impact of Bacille Calmette-Guérin (BCG) vaccination history of donor PBMCs on the immune responses to Mtb infection. Aggregates of PBMCs were initially observed on day 3 and the size of aggregates continued to increase on day 8 post-infection, where macrophages and T cell subsets were identified to be present. Similarly, mycobacterial load progressively increased in infected PBMCs during the 8 days of culture but were significantly lower in infected PBMCs from BCG vaccinated (BCG+) donors compared to unvaccinated (BCG-) donors. The levels of INF-γ, TNF-α, IL-4, IL-6, IL-10 and IL-17 in the supernatants of Mtb-infected PBMCs peaked at day 3 and decreased on days 5 and 8. The levels of these cytokines except IL-10 were significantly lower in Mtb-infected PBMCs from BCG+ donors compared to infected PBMCs from BCG- donors. The percentages of activated naïve Th cells, activated effector memory Th cells and activated central memory Tc cells were significantly higher in Mtb-infected PBMCs compared to uninfected PBMCs at day 8 post-infection. Further, the proportion of activated central memory Tc cells was significantly higher in infected PBMCs from BCG+ donors compared to the BCG- donors. This study highlights the possibility that BCG vaccination may confound results that utilize human PBMCs to study Mtb infection.
Keyphrases
- mycobacterium tuberculosis
- pulmonary tuberculosis
- immune response
- induced apoptosis
- peripheral blood
- endothelial cells
- cell cycle arrest
- rheumatoid arthritis
- kidney transplantation
- dendritic cells
- stem cells
- signaling pathway
- systemic lupus erythematosus
- toll like receptor
- bone marrow
- hepatitis c virus
- single cell
- disease activity
- human immunodeficiency virus
- idiopathic pulmonary fibrosis
- inflammatory response
- cell therapy
- adverse drug
- pi k akt
- antiretroviral therapy