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How is Leishmania transmitted?

Sandfly vectors -




Old world - Phlebotomus species




New world - Lutzomyia species

Leishmania

Obligate intracellular single-celled parasite




Many species




Can be transmitted across wide range of mammals

Infective and non-infective stages of leishmania

Amastigotes


Non-infective promastigotes


Metacyclic, infective promastigotes

What cells do leishmania infect/invade?

Cells of the macrophage lineage.

Morphology of amastigotes

Rounded (loses flagellum once inside macrophages)





Morphology of promastigotes

Long and slender and has one flagellum


20-25 um including flagellum




Increased expression of surface molecules: GP633, LPG, GIPLS

Some examples of mammals in which Leishmania can live and be transmitted

Rodents, Dogs, Sloths

Clinical manifestations you can see and what its caused by

Skin sores:


on ears, face, nose




Proliferating mass of macrophages

The three types of molecules on the surface of metacyclic promastigotes and their purpose

To prepare for host-cell invasion




Lipophosphoglycan - Inositol lipid anchor of glycocalyx




Family of glycoinositol phospholipids




GIPLs - gkycosylphosphatidylinositol anchored proteins - surface protease

How promastigotes attach to macrophages

LGP and GP63 attach directly to via mannose fucose receptor or via complement componenets : CR1 and CR3

Why aren't promastigotes destroyed? (outside of cell)

Shed and elongates LPG (parasites thicker)




Increased GP63 - cleaves C3b to inactive form




LPG + GP63 interact with complement receptor -> prevents macrophage from becoming a killing cell

How parasite survives in macrophage

Parasitophorous vacuole -> pH4.2 - 5.2 LPG inhibits lysosomal enzymes




GP63 inactivates host proteases (esp at pH4




LPG inhibits PKC (involved in generating toxic metabolites in macrophages)