Leishmania development in sand flies: parasite-vector interactions overview

Abstract

Leishmaniases are vector-borne parasitic diseases with 0.9 - 1.4 million new human cases each year worldwide. In the vectorial part of the life-cycle, Leishmania development is confined to the digestive tract. During the first few days after blood feeding, natural barriers to Leishmania development include secreted proteolytic enzymes, the peritrophic matrix surrounding the ingested blood meal and sand fly immune reactions. As the blood digestion proceeds, parasites need to bind to the midgut epithelium to avoid being excreted with the blood remnant. This binding is strictly stage-dependent as it is a property of nectomonad and leptomonad forms only. While the attachment in specific vectors (P. papatasi, P. duboscqi and P. sergenti) involves lipophosphoglycan (LPG), this Leishmania molecule is not required for parasite attachment in other sand fly species experimentally permissive for various Leishmania. During late-stage infections, large numbers of parasites accumulate in the anterior midgut and produce filamentous proteophosphoglycan creating a gel-like plug physically obstructing the gut. The parasites attached to the stomodeal valve cause damage to the chitin lining and epithelial cells of the valve, interfering with its function and facilitating reflux of parasites from the midgut. Transformation to metacyclic stages highly infective for the vertebrate host is the other prerequisite for effective transmission. Here, we review the current state of knowledge of molecular interactions occurring in all these distinct phases of parasite colonization of the sand fly gut, highlighting recent discoveries in the field.

Figure 1

Development of Leishmania in the sand fly digestive tract. Sand fly midgut is composed of a single layered epithelium with a brush border of microvilli lining the lumen. In contrast, the foregut (including the stomodeal valve) and the hindgut (including the pyloric triangle) are lined by chitin. Amastigotes (a) ingested along with a bloodmeal into abdominal midgut transform into procyclic promastigotes (b), these replicate and transform to long nectomonads (c). During the bloodmeal digestion the parasites are surrounded by peritrophic matrix (PM). When the PM is broken by sand fly enzymes, long nectomonads escape through the posterior opening and attach to midgut microvilli. The next stage are replicative short nectomonads called leptomonads (d); these transform into infective metacyclic promastigotes (e) or attach to the chitin lining of the stomodeal valve as haptomonads (f). In the late-stage development, masses of nectomonads secreting filamentous proteophosphoglycan obstruct the thoracic midgut. This, together with destruction of the valve, facititates reflux of parasites when the fly takes a subsequent bloodmeal. In subgenera Viannia and Sauroleishmania, haptomonads attach also to chitin lining of the pylorus region.