Sara Dabirian, Ph.D student at Pasteur Institute of Iran, took advantage of molecules with limited toxicity to stimulate innate immune responses as a new approach to fight against leishmaniasis. Human neutrophil peptide-1 (HNP-1) is one of the most potent defensins with a broad antimicrobial activity. This peptide is naturally found within a granule of human neutrophils, a cell type that has the capacity to both kill Leishmania parasites and serve as an immediate host cell.

Using a prokaryotic expression system and an in vitro folding procedure, Dabirian et al. succeeded to cost-efficiently produce substantial amounts of active HNP-1.

The results, publishing October 17th, 2013 in PLOS Neglected Tropical Diseases, demonstrated that HNP-1 has direct leishmanicidal effects for both promastigote and amastigote and efficiently kills the parasites at concentrations non-toxic to host cells. Treatment of neutrophils with the HNP-1 was further shown to increase the life-span of the neutrophils and reduce the ability to be infected by Leishmania parasites. This was accompanied by an increase in production of the cytokine TNF-α and a reduction of the regulatory cytokine TGF-β following HNP-1 treatment of Leishmania infected neutrophils.

Professor Sima Rafati, from Molecular Immunology and Vaccine Research Laboratory at Pasteur Institute of Iran, who led the study, said: "The effects of HNP-1 on parasites and infected cells are anticipated to favorably alter the outcome of Leishmania infection. These results showed that HNP-1 holds a real potential as a candidate for a new modality of treatment for leishmaniasis." This approach may also be applicable for treatment of different forms of leishmaniasis, although it needs further investigation both in vivo and in vitro.