taxonomy of helminths
- nematodes (roundworms)
- platyhelminthes (flatworms)
- trematodes (flukes)
- cestodes (tapeworms)
What is the GI host response to helminths?
- Th2 CD4+ cells
- IL-5 recruiting eosinophils
- IL-4/IL-13 support B cell production of IgE
- effector cells: mast cells, eosinophils & goblet cells
Name parts of helminth-induced pathology
- successful parasite lives in host
- disease mostly depends on host factors
- protozoa multiply in host, most others don‘t
- direct tissue destruction
- hypersensitivity reactions common
- eosinophilia
Name three intestinal helminths and their related experimental model
- Strongyloides stercoralis - strongyloides ratti
- human hookworm (ancylostoma duodenal) - Nippostrongylus brasiliensis
- Schistosomia spp. - Schistosomia mansoni
hookworm model (with life cycle)
- Nippostrongylus brasiliensis
- definitive host: rodents
- not infective for human -> no biosafety level
- life cycle: larvae penetrates skin -> lung -> pharynx -> adults in gut —> eggs in feces
How do you get L3 larvae of N. brasiliensis to infect mice?
- propagation in rats (bigger)
- feces is collected an incubated
- infection by s.c.
How to analyse N. brasiliensis infection in mice?
- Analysis 7-14 dpi (WT can clear infection completely)
- worm (intestine) and egg (feces) count (eggs flout on surface of buffer)
- staining of intestine
- IgE in serum
- Th differentiation
BALB/c vs IL-4Rα-/- mice in n. brasiliensis infection
- BALB/c can clear infection, IL-4Rα-/- are susceptible
- IL-4Rα-/- have reduced Th2 response
- IL-4Rα-/- have reduced levels of IgE in serum
IL-4Rα-/- have no IL-4 and IL-13 and no protection
Facts about Strongyloides stercoralis
- 2 unique life cycles (free and parasitic)
- 30-100 million infections annually
- Filiariform penetrates skin (contaminated soil)
- larvae migrate into lung and are than swallowed
Pathology of S. stercoralis infection
- invasive: skin penetration
- pulmonary: during migration
- intestine: tissue destruction
- hyperinfections possible (anemia, cough, diarrhea, …)
- can lead to death in immunocompromised individuals
Describe the life cycle of S. ratti
females in mucosa of small intestine -> lay eggs -> eggs in feces shed in environment -> hatching
- male develop into free-living adult
- female develop into free-living adult or
- female develop direct into infective L3 larvae
How does the S. ratti model work?
- model for S. stercoralis
- not infective for humans
- L3 larvae maintained trough serial passaging
- infection s.c. or percutaneous in buffer drop
Detection of S. ratti
- dose dependent
- low (6 larvae) s.c. similar to natural percutaneous route
- egg count via qPCR (28S rRNA)
- adult count in small intestine
What is the S. ratti induced immune response?
- nematode specific Th2
- Th1 is reduced
Schistosoma spp.
- flatworms
- 4 species
- S. mansoni
- S. japonicum
- S. haematobium
- S. indicum
- Schistosomiasis affects 207 million annually (50% symptomatic)
life cycle of Schistosoma spp.
eggs in water -> larvae -> into snail -> larvae in water -> penetrate human skin -> migrate to lymphatic system -> travel to lung (70% are eliminated) -> migrate into liver -> maturation in liver -> migrate into target tissue:
- S. mansoni: mesentric venules of large bowel and rectum
- S. japonicum: mesentric veins of small intestine
- S haematobium: perivesical venous plexus of bladder
50% of eggs stay in tissue, 50% exit body
Schistosoma spp. model
- S mansoni -> infectious for human BSL 3
- mince egg containing tissue -> eggs will float on water and hatch
- incubate snails with phototropic miracidia
- keep snails in dark; for cercariae shedding snails in strong light
mice infection via natural route -> place mouse foot in cercariae suspension
- Which Interleukin deficiency enhances mice survival during S. mansoni infection?
- Which Interleukin deficiency enhances Th1 response?
1.
IL-13
IL-4 induces mortality, same as IL-4-/- IL-13-/- (more eggs in intestine & less in feces)
- IL-4/IL-13 deficiency, it also diminishes fibrosis
