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Playing hide and seek with the immune system, the Salmonella way

In a recent study, researchers at the Indian Institute of Science, Bengaluru, have described how the pathogenic bacteria Salmonella, which causes a range of diseases from diarrhoea to typhoid, escapes from our immune system. The findings of this study, funded by the Department of Biotechnology and the Department of Atomic Energy, have been published in the journal PLoS Pathogens.

Salmonella is a smart bacteria that has many tricks in its kitty to evade the action of our immune system—the de facto protector of our body. Once they escape, these bacteria become very strong, making it difficult to treat them. Although Salmonella can attack many types of cells in our body, the dendritic cells—a kind of cells in our immune system—play an essential role in the infection. In this study, the researchers unfold the action of the bacteria in the dendritic cells.

The researchers used mice models in their experiments and demonstrated that in the dendritic cells, Salmonella enhances the expression of a protein sirtuin 2 (SIRT2). Although previous studies have explored the potential role of sirtuin 2 in other cases like oxidative stress, tumour growth and inflammation, its involvement in Salmonella infection was not yet known.

When the sirtuin 2 is produced in excess, a chain of events is initiated. Increase in sirtuin 2 enhances the production of nitric oxide in the cells by increasing an enzyme called nitric oxide synthase, which produces nitric oxide. Although nitric oxide has antibacterial properties, it weakens the immune system of the host by inhibiting the multiplication of T cells, an important member of the immune system.

“Being a suppressor of T cell proliferation as well as an antimicrobial agent, nitric oxide regulation can affect Salmonella infection in both positive and negative ways, respectively”, explain the authors.

However, not everything is bad! The researchers found a potential solution to the problems caused by sirtuin 2. They observed that by artificially inhibiting the action of sirtuin 2, the immune cells in the host could be made fit enough to clear the pathogens. “Our study demonstrates that sirtuin 2 deficiency lowers the systemic bacterial burden as well as prolongs survival of infected mice,” add the authors.

The researchers also believe that their findings might help design new strategies to control the Salmonella infection.

“Considering all the available data, administration of sirtuin 2 inhibitor or nitric oxide synthase 2 inhibitor, along with conventional antibiotics, might be helpful in clearing persistent infection”, conclude the researchers.