title: Human chemokines as antimicrobial peptides with direct parasiticidal effect on Leishmania mexicana in vitro.
abstract: Chemokines and chemokine receptor-mediated effects are important mediators of the immunological response and cure in human leishmaniasis. However, in addition to their signalling properties for leukocytes, many chemokines have also been shown to act directly as antimicrobial peptides on bacteria and fungi. We screened ten human chemokines (CXCL2, CXCL6, CXCL8, CXCL9, CXCL10, CCL2, CCL3, CCL20, CCL27, CCL28) for antimicrobial effects on the promastigote form of the protozoan parasite Leishmania mexicana, and observed direct parasiticidal effects of several, CCL28 being the most potent. Damage to the plasma membrane integrity could be visualised by entrance of propidium iodide, as measured with flow cytometry, and by scanning electron microscopy, which showed morphological changes and aggregation of cells. The findings were in concordance with parasiticidal activity, measured by decreased mitochondrial activity in an MTT-assay. This is the first report of direct antimicrobial activity by chemokines on parasites. This component of immunity against Leishmania parasites identified here warrants further investigation that might lead to new insight in the mechanisms of human infection and/or new therapeutic approaches.
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden. sara.karlsson_sobirk@med.lu.se
authors.forename: Sara K
authors.initials: SK
authors.lastname: Söbirk
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Arne
authors.initials: A
authors.lastname: Egesten
authors.forename: Paul
authors.initials: P
authors.lastname: Bates
authors.forename: Oonagh
authors.initials: O
authors.lastname: Shannon
authors.forename: Mattias
authors.initials: M
authors.lastname: Collin
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D000977:Antiparasitic Agents / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000494:pharmacology; D054418:Chemokine CCL20 / Q000494:pharmacology; D054425:Chemokine CCL27 / Q000494:pharmacology; D054405:Chemokine CCL3 / Q000494:pharmacology; D054357:Chemokine CXCL10 / Q000494:pharmacology; D054426:Chemokine CXCL2 / Q000494:pharmacology; D054427:Chemokine CXCL6 / Q000494:pharmacology; D054370:Chemokine CXCL9 / Q000494:pharmacology; D018925:Chemokines / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D007894:Leishmania mexicana / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D000977:Antiparasitic Agents; D018932:Chemokine CCL2; D054418:Chemokine CCL20; D054425:Chemokine CCL27; D054405:Chemokine CCL3; D054357:Chemokine CXCL10; D054426:Chemokine CXCL2; D054427:Chemokine CXCL6; D054370:Chemokine CXCL9; D018925:Chemokines; D016209:Interleukin-8; D010455:Peptides