A10 - Microbial parasites of mucosal surfaces

What are the three major enteric protozoa found in the human gut microbiota?

• Entamoeba

  • Extracellular parasite

• Giardia

  • Extracellular parasite

• Cryptosporidium

  • Intracellular parasite

Where is Entamoeba histolytica found in the gut?

Found in the lumen of the large intestine

• Most people infected are usually asymptomatic

What disease can Entamoeba histolytica cause?

Amoebiasis or Amoebic dysentery.

• Parasitic infection of the intestines caused by Entamoeba histolytica

• Leads to diarrhoea, abdominal pain and can even spread to other organs in severe cases

How is Entamoeba histolytica transmitted?

Via oral ingestion of the cyst form of Entamoeba histolytica.

What is the life cycle of Entamoeba histolytica?

Cyst will pass through the stomach before excysting and replicating via binary fission

Entamoeba histolytica then transforms into the trophozoite form

These Trophozoite forms will die rapidly in the external environment but can thrive inside the GI tract

When conditions in the GI tract are unfavourable, it will transform back into the cyst form and lay dormant

How does Entamoeba histolytica cause tissue damage?

Binds to host cell receptors and induces contact-dependent killing

• This may involve cytotoxins

The killed cells are then ingested by Entamoeba histolytica

Entamoeba histolytica can kill and ingest which immune cells?

Can kill and ingest neutrophils and non-activated macrophages

• This is unique as the phagocytes are ingested by the parasite

Elevated levels of P. copri have what effect on Entamoeba histolytica infections?

P. copri is associated with severe inflammation and therefore can modulate Entamoeba histolytica infection outcome.

• Can cause Entamoeba histolytica infection to be symptomatic

E. coli serotype O55 is unique in what way?

Has a surface carbohydrate composition rich in galactose and N-acetyl galactosamine

How can E.coli O55 impact Entamoeba histolytica infection?

Gal/GalNAc lectins on Entamoeba histolytica bind strongly to E.coli O55

This triggers

• Activation of downstream pathways including regulation of

  • Phagocytosis

  • Proteolysis

  • Adhesion

  • Cytotoxicity

What is the Bone Marrow-derived dendritic cell (BMDC) mechanism of Segmented Filamentous Bacteria (SFB) amoebiasis protection?

BMDCs from SFB-colonised mice secreted significantly higher amounts of IL-23

• This induces IL-17A secretion and induces neutrophils

• This is important in amoebiasis immunity

What is the DAMPs mechanism of Segmented Filamentous Bacteria (SFB) amoebiasis protection?

SFB sera contained increased host DAMPs and Serum amyloid A (SAA)

These cause an increase in

• Granulocyte monocyte precursors (GMPs) which raises intestinal neutrophil count

• This is important in amoebiasis immunity

What disease does Giardia lamblia cause?

Giardiasis 

How is Giardia lamblia  transmitted?

Cysts are ingested through contaminated water/food

What is Giardia lamblia’s life cycle?

pH of the stomach causes a developmental trigger and Giardia lamblia excysts

• This releases two trophozoites per cyst

Once in the small intestine, the trophozoites replicate by binary fission

The trophozoites remain in the lumen of the small bowel where they are either free floating or attached to the mucosa

Once they enter the colon, a second developmental trigger causes them to transform back into cysts

How do Giardia lamblia symptoms compare to E. histolytica?

Generally only mild and localised tissue damage with no tissue invasion

• 50% of individuals are also asymptomatic with most recovering within 14 days

How does Giardia lamblia damage villi and what can this cause?

Damages them due to the ventral sucking disk

• They use this to attach to the mucosa

Damage to villi can result in malnutrition as absorption of nutrients will be impaired

How does Lactobacillus johnsonii impact Giardia lamblia infection?

• Results in inhibition of Giardia lamblia proliferation

• Inhibits colonisation of the gut by Giardia lamblia  

• Causes increase in antibody responses and reduce parasite-mediated mucosal damage

Co-inoculation of E. coli/Human microbiota with Giardia lamblia allow C. elegans to thrive.

True or False?

False.

Co-inoculation of E. coli/Human microbiota with Giardia lamblia is deadly for C. elegans

Giardia lamblia has been shown have what effect on the intestinal microbiota in vitro?

Giardia lamblia has been shown to increase virulence of intestinal microbiota towards human epithelial cells

Cryptosporidium contains what unique organelle?

Cryptosporidium contains the apicoplast

• Considered essential for the survival of Cryptosporidium

• Performs many metabolic functions (e.g. lipid biosynthesis and iron metabolism)

What disease does Cryptosporidium parvum cause?

Cryptosporidiosis

How can symptoms differ between immunocompetent and immunocompromised individuals?

In immunocompetent individuals: Cryptosporidium parvum can cause transient diarrhoea

In immunocompromised individuals: Cryptosporidium parvum can cause severe chronic disease

Cryptosporidium parvum can multiply and survive outside of cells and mainly inhabits the GI tract.

True or False.

False.

Cryptosporidium parvum is an obligate intracellular parasite which needs to invade host cells to multiply

How does Cryptosporidium parvum cause cell damage/death?

Parasite invasion and multiplication

Epithelial cell extrusion

• Cells are removed from the epithelial layer by ‘squeezing them out’

T-cell mediated inflammation

How did SCID mice show that Cryptosporidium parvum resistance is mediated by the microbiota and not the immune system?

Germ-free SCID mice had a heavy infection after 3 weeks

However, normal microbiota SCID mice only had a light infection

• Took 6 weeks for parasites to be readily detected

Important to note that T-cell responses are still key for recovery from infection

Susceptibility to Cryptosporidium parvum positively correlates with abundance of Indole-producing bacteria.

True or False?

False.

Susceptibility to Cryptosporidium parvum inversely correlates with abundance of Indole-producing bacteria.

What are potential ways Indole may protect against Cryptosporidium parvum infection?

• Indole may target parasites and inhibit/kill them

• Indole may trigger host tissue/immune responses against Cryptosporidium parvum