Leishmaniasis

Question 1

Describe the protein coat of Leishmania

Answer 1

LPG (lipophosphoglycan)
GPI anchored
CRP acts as an alternative opsonin for L.donovani

Question 2

How does LPG affect the immune system?

Answer 2

IL-12 production inhibited
Inhibition of phagosome formation and chemokine function
Stimulates inhibitory chemokines
Acts as ligand for iNKT cells

Question 3

What are the effects of promastigote secretory gel on parasite survival?

Answer 3

PSG enhances infectivity by recruiting macrophages and aiding survival

Question 4

Describe the Trojan Horse theory of Leishmania invasion

Answer 4

L engulfed by neutrophils, become apoptotic, neutrophils engulfed by macrophages. Amastigotes transferred.

Certain recpetors on neutrophils deactivated by L to avoid triggering inflammation response from macrophage

No experimental evidence of macros taking up neutrophils

Question 5

Describe how L survives in the phagosome

Answer 5

Neutrophils - need to avoid tertiary and specific granules
Dendritic cells - immature = survival, mature = death mediated by RAB7

L donovani inhibits pahgosome maturation via an actin shell (around phagosome) which prevents V-ATPase from binging and impairs NADPH oxidase assembly

Question 6

Describe how L competes for nutrients in the phagolysosome

Answer 6

Iron- Amastigote adds transporters to membrane of phagolysosome
IRON1: Scl11a1 - iron transporter regulates efflux out of phagolysosome
IRON2: Co-op between LIT1 (ferrous iron transporter) and LFR1, ferric iron reductase for L survival

Question 7

Describe how L. modifies macrophage signal transduction pathways

Answer 7

Inhibits PKC, promotes/controls JAK/STAT pathways (production of cytokines)