Potential therapy for Kala-azar
doi:10.1038/nindia.2019.1 Published online 10 January 2019
Researchers have gained new insights into how Kala-azar-causing parasites proliferate inside the specific immune cells of a host by evading its immune system1. They identified that the parasites suppress the host’s immune system by blocking the activity of a specific enzyme that usually helps kill parasites through inflammation.
These insights will help design new drugs for treating Kala-azar, a disease that is difficult to treat with existing antimicrobial drugs.
In recent years, Leishmania donovani, the parasite that causes Kala-azar, has developed resistance to existing antimicrobial drugs. The key to such drug resistance is its ability to protect itself against the onslaught of the host’s immune cells, such as macrophages, known to kill microbes. However, it is still unclear how the parasites evade a host’s immune system.
To decipher exactly how the parasites avoid the attack of the host’s immune cells, scientists from the Indian Institute of Technology in Guwahati, the Indian Institute of Technology Varanasi and the Banaras Hindu University in Varanasi studied the interactions between the parasites and specific host immune cells in infected blood cells isolated from patients.
The team, led by Vikash Kumar Dubey, found that the parasites blocked the formation of a specific inflammosome, a multiprotein complex that activates the host’s immune cells. The parasites significantly inhibited the activity of caspase 1, a key enzyme that triggers cell death through inflammation.
The study could provide leads for developing molecules that may rob the parasites of their ability to suppress the host’s immune system, says Dubey.
1. Saha, G. et al. Leishmania donovani evades caspase 1 dependent host defense mechanism during infection. Int. J. Biol. Macromol. 126, 392-401 (2019)