Authors
E Giraud4; T Derrick4; O Martin4; R Dillon3; T LestinovaP VolfI Muller2; P Bates3; M E Rogers4; 1 Charles University, Czech Republic; 2 Imperial College; 3 Lancaster University; 4 London School of Hygiene and Tropical Medicine Discussion
The promastigote secretory gel (PSG) is matrix of filamentous proteophosphoglycan secreted by Leishmania promastigotes inside the sand fly gut, which facilitates the transmission and infection of the mammalian host. The early host response to PSG has not been characterised.
Mice were inoculated with 1000 Leishmania mexicana metacyclic promastigotes into BALB/c mouse ears, with or without PSG. The Affymetrix Mouse GeneChip revealed differential expression of 7,927 transcripts (FC >1.5, 5% FDR) to PSG, i.e. 27% of the mouse genome. We found that PSG was associated with an early up-regulation of transcripts involved in inflammation, inflammatory cell recruitment, epithelial cell proliferation and fibrosis. In vitro and in vivo experiments revealed that PSG significantly accelerated wound healing. Insulin-like growth factor 1 (IGF1) is linked to macrophage alternative activation and wound repair. Dermal expression of IGF1 was enhanced following an infected sand fly bite and was acutely responsive to the PSG but not to parasites or sand fly saliva. Antibody blockade of IGF1 ablated the gel’s ability to promote wound closure in mice and significantly reduced the virulence of L. mexicana infection delivered by sand fly bite.
These results show that PSG strongly influences multiple stages of the wound healing process in skin following Leishmania transmission; resulting in accelerated healing and, vi 
