Carrier or patient?
When an immune cell and a bacterium meet, there can be several outcomes: the immune system kills the bacterium, the bacterium overcomes the immune defense, or, in the case of diseases such as tuberculosis, the bacterium can be inactive for years, causing the disease much later, and sometimes remaining dormant forever.
When macrophages (blue) meet bacteria (red), the first 1-2 days are crucial for the final result. Source: Weizmann Institute of Science.
Researchers from the Weizmann Institute have suggested that the fate of the interaction of bacteria with the immune system is decided quite early – within 24-48 hours after infection. The hypothesis was tested on blood samples taken from healthy volunteers, into which salmonella was injected in laboratory conditions, registering an immune response. The researchers used an RNA sequencing technique to determine the activity of genes in thousands of individual immune cells. They were able to see the reaction of each blood cell after meeting with salmonella and determine the activation profiles of each of them. This allowed us to identify patterns that cannot be obtained in standard laboratory tests.
Comparison with existing genomic analysis methods showed that standard methods did not reveal differences between the groups, while the algorithm developed by the group revealed a difference that determined the ability to destroy bacteria.
However, RNA sequencing of individual cells is only available to specialized laboratories. The group wondered if there was a way to link the results to real-time blood tests in real patients. To do this, they turned to databases of immune responses to salmonella and developed an algorithm that allowed extracting similar information from available databases. The algorithm uses the information obtained from a standard blood test and extrapolates it to the properties of individual blood cells. It not only helps to determine the reaction of the immune cells involved in the response, but also to identify the level of their activity and, consequently, the potential strength of the immune response.
To check whether the same algorithm can be used to diagnose tuberculosis, the causative agent of which can be dormant in the human body for years, the researchers turned to another database that tracked tuberculosis patients and carriers for two years. They applied the algorithm to the blood test results in both groups, as well as in a subgroup of patients who switched from carrier to disease.
Researchers have found that monocyte activity levels can be used to predict the onset or course of the disease. Despite the fact that the algorithm was created on the reaction of immune cells with salmonella, which cause a completely different type of disease, the researchers were able to predict in advance which of the carriers will develop an active form of tuberculosis.
When symptoms of tuberculosis appear, patients have to take three different antibiotics for nine months, and resistance to them has begun to spread. If patients at risk of an active form of the disease are identified in advance when the bacterial load is several times less, their chances of recovery will be much higher. And public health systems in countries where tuberculosis is an endemic disease could reduce the incidence rate while reducing the cost of treatment.
The researchers intend to continue working in this direction and expand their own database on the causative agent of tuberculosis and other microorganisms in order to improve the algorithm and develop tools that can be used to predict morbidity.
Article by N. B. Ben-Moshe et al. Predicting bacterial infection outcomes using single cell RNA-sequencing analysis of human immune cells is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Weizmann Wobder Wander: First Impressions Go a Long Way in the Immune System.