parasite-vector immune interaction Flashcards
1
Q
mosquito immunity in the midgut
A
- ideal place to target malaria parasite
- narrow bottleneck
- fewer parasites to target
- fewer genomes to develop resistance
- some wild anopheles strains resistant:
- lyse plasmodium in gut
- melanise plasmodium in gut
2
Q
Imd pathway
A
- known in drosophila, but mosquitoes?
- RNAi to silence pathway
- Rel2 and PGRP-LC silencing (Imd TF and receptor)
- increased susceptibility to bacterial infection
- same as drosophila
- similar with toll
- same with infected children’s blood and falciparum
- but PGRP-LC recognises PG? (bacterial)
- inactivated rel2 → higher oocyst numbers of P. berghei
3
Q
PGRP-LC and plasmodium
A
- PGRP-LC recognises PG on bacterial surface
- plasmodium has few glycosylated proteins
- won’t be recognised
- must be connection with bacteria
- bloodmeal is good environment for gut bacteria proliferation
- huge increase in bacteria numbers in gut
- stimulates Imd to create anti-bacterial and anti-plasmodium effectors without parasite recognition
4
Q
Toll pathway in mosquitoes
A
- orthologs identified but no clear receptor
- Rel2 only involved (bacterial infection)
- Rel1 involved in fungal
5
Q
Rel1 and parasitic infection
A
- RNAi inactivated Rel1
- no difference compared to control
- inactivate cactus as well → constitutive pathway activation
- all parasites melanised and killed
- normal conditions → no effect of Rel1
- constitutive activation → killing
- create transgenic mosquitoes?
- diminished fitness by constitutive activation?
6
Q
Duox pathway
A
- bacteria recognised in gut → activated in gut → ROS production
- hydrogen peroxide produced
- substrate for immune peroxidase
7
Q
IMPer
A
- immune peroxidase
- cross-links proteins produced in lumen outside gut cell → proteinaceous layer
- prevents PG from penetrating
- no contact with PGRP-LC
- bacterial tolerance if levels not too high
- bacteria are necessary
8
Q
IMPer/Duox inactivation
A
- no proteinaceous layer formation
- immune system hyperactivation
- parasite and bacterial killing
- exploit to combat malaria?
9
Q
haemolymph immune response
A
- mainly complement
- ookinete invaded cell death by apoptosis as defence mechanism
- apoptosis activated by JNK pathway
- heme peroxidase and nitric oxidase activated
- ROIs attack cell and parasite
- parasite on other side recognised and lyses by Tep1
- ~20% survive
10
Q
Tep1
A
- opsonin, acts like C3
- coats pathogens → promote phagocytosis
- lacks anaphylotoxin domain of C3 (formation of C3a)
- open circulation?
- no need for long distance communication with other tissues via anaphylotoxic reactions
- open circulation?
- thioester motif binds pathogen surface
- exposed by cleavage
- requires LRIM1 and APL1C
11
Q
LRIM1/APL1C
A
- leucine-rich repeat immune protein 1
- APL1C also leucine-rich repeat protein
- complex together
- leu-rich repeats form petal-like structure
- maybe involved in recognition
- coiled-coil cargo domain carreis Tep1
- deposits on pathogen surface
- inactivate either protein → complement inactivation → increased susceptibility
12
Q
mosquito complement pathway
A
- Tep 1 circulates in haemolymph
- cleaved and activated
- binds LRIM1/APL1C complex
- if not, reacts with water → inactivated
- delivery to parasite surface
- complex liek C3 convertase forms
- more Tep1 activated and binds → lysis
- also C-type lectin receptor complex
- unknown mechanism
13
Q
Tep1 variation
A
- M form in agricultural land
- rB resistant Tep1 allele at high frequency
- fewer bacteria in temporary puddles of S form
- decreased advantage of rB allele as decreased risk of bacterial infection → s allele
- less resistant to parasites
14
Q
melanisation
A
- form of parasite kiling when it can’t be lysed
- e.g. philaria worm
- mediated by LRIM1
- inhibited by CTL4
15
Q
CTL4
A
- C-type lectin 4
- if inactivated all parasites melanised
- lysis usually default outcome
- works together with complement
- potential way of preventing transmission
- but could reduce fitness
