Researchers have used single-cell RNA sequencing to study the initial processes involved in infection with Mycobacterium tuberculosis (Mtb), which causes tuberculosis, and have provided new insights into the infection process that could potentially lead to new treatments for the disease.
Mtb latently infects around a quarter of the world’s population. With latent infection, individuals do not have symptoms, do not feel sick, and are not infectious. In contrast, symptoms are experienced in active pulmonary tuberculosis and individuals do transmit the Mtb. The immune system mechanisms involved in the progression from latent to active pulmonary infection are poorly understood.
Researchers at the Southwest National Primate Research Center (SNPRC) at the Texas Biomedical Research Institute developed a novel approach, dubbed ScRNAseq, that allowed them to study the immune response to infection with Mtb at a much higher resolution than as previously possible.
Non-human primates mirror both latent and active pulmonary TB in humans. The researchers infected macaques with Mtb and used their new technique to study infection and characterize the lung immune landscape with both latent and active pulmonary TB in high throughput studies.
The researchers identified an immune response to infection with Mtb in single lung cells when the infection progressed to disease and when infection did not. In active pulmonary TB in macaque lungs, the researchers identified three key features: There was a large influx of plasmacytoid dendritic cells in response to infection with Mtb, an interferon response, and activated T cell response. In contrast, with latent infections there was an accumulation of CD27 + Natural killer (NK) cells in the macaque lungs as well as in the circulation of latent Mtb macaques.
Plasmacytoid dendritic cells are immune cells that are sent out to prevent bacteria and viruses from replicating. The researchers found that the plasmacytoid dendritic cells overproduce Type 1 interferons when infection is detected, and instead of the interferon response controlling the infection, the interferon response correlated with disease progression.
“When we have a more precise understanding of how an infection develops, that knowledge can lead us to identify new drugs or therapies to treat disease and improve vaccines,” Kaushal said. “Although our findings decreased the gap in knowledge of TB disease and latent infection, there is still more we need to learn.”
You can read more about the research in the paper – The immune landscape in tuberculosis reveals populations linked to disease and latency – which was recently published in the Cell Host & Microbe. DOI: 10.1016/j.chom.2020.11.013