Leishmaniasis or kala azar is a disease caused by the parasite Leishmania, which belongs to lower eukaryotes. The bite of an insect Lutzomyia longipalpis aids in the transmission of the parasite to complete its life cycle.
In earlier studies it has been shown that the components of saliva (like hyaluronidase) from this arthropod aid in the transmission of Leishmania in host systems. However authors here have shown that another protein Lundep is also an active constituent of saliva for enhancing the parasite infection.
Since the first line of defense is by neutrophils and it has been established in case of Leishmaniasis that the parasites dodge this line of defense by entering into the compartments that are nonlytic or by dodging neutrophil extracellular traps (NETs). Salivary Gland Extracts (SGE) from Lutzomyia longipalpis are known to support parasite survival inside the neutrophils, however still less is known about the NETosis or NET formation in respose to Leishmania parasite.
Lundep (Lutzomyia NET destroying protein), a female specific endonuclease has been shown in this study to have enhancing effect on the infectivity as well as inhibitory effect on intrinsic coagulation pathway. It has been demonstrated that catalytic activity of the salivary endonuclease is accountable for enhancing infectivity or in aiding parasites escape from NETs.
This study has shown that Lundep:-
- Aids in degradation of the DNA scaffold of NETs. [Lundep has a DNase activity of about 300000 Kunitz units per mg of protein and can hydrolise both single stranded and double-stranded DNA.]
- Protects parasites from leishmanicidal activity of NETs.
- Promotes survival of promastigotes.
- Prevents blood coagulation while insect biting. [ Lundep is shown to have DNase activity that promotes antithrombotic effects]
- Assists in taking blood meal by decreasing the viscosity at the site of bite. [At the site of bite viscosity augments due to host DNA release]
So far no vaccine is available for Leishmaniasis (kala azar) and the authors consider Lundep as a potential target for vaccine generation.
Lundep, a Sand Fly Salivary Endonuclease Increases Leishmania Parasite Survival in Neutrophils and Inhibits XIIa Contact Activation in Human Plasma. Andrezza C. Chagas, Fabiano Oliveira, Alain Debrabant, Jesus G. Valenzuela, José M. C. Ribeiro, Eric Calvo. DOI: 10.1371/journal.ppat.1003923