Lecture 6 - Host-microbiota interactions at mucosal surfaces

What are neurotransmitters?

Messengers which transmit signals from nerve cells to target cells

What are Hormones?

Messengers which are secreted by endocrine glands and travel in the blood stream

• Sending messages across the body

How can the microbiota communicate with host cells?

Microorganisms can synthesise and respond to hormone and neurotransmitters

• This allows them to influence host cells

• These molecules can also influence growth and virulence of microorganisms

Potentially how is the gut able to influence the brain and brain health?

The gut microbiota can synthesise SCFAs and neurotransmitters

• These can enter the blood and travel to the brain where they influence host cells

Cortisol has pro- or anti-inflammatory properties?

Cortisol has anti-inflammatory properties.

What anti-inflammatory roles does cortisol have?

• Supresses neutrophil functions

• Supresses classical macrophage function

• Reduces number of B-cells

  • Inhibits IgG but promotes IgE

• Elevates IL-10 expression 

  • Anti-inflammatory cytokine

• Inhibits T helper cell function through downregulation of cytokines

How can chronic high cortisol levels lead to inflammation?

Can result in desensitisation to cortisol

• This drives a pro-inflammatory response rather than the typical anti-inflammatory response

  • Because anti-inflammatory pathways become desensitised 

Acetylcholine is a cytotransmitter. What is that?

Allows cell-cell communication

How was the Cholinergic Anti-inflammatory Pathway discovered?

Concept was developed due to the discovery of ChAT+ T-cells

• Following activation by norepinephrine, they begin releasing ACh and migrate around the body

T-cell derived ACh can act on numerous other immune cells via which receptor?

a7nAChR receptor 

• Alpha 7 Nicotinic Acetylcholine receptor

What effect does T-cell derived ACh binding to a7nAChR have on immune cells?

Downregulates their expression of inflammatory mediators

• Anti-inflammatory 

In the intestine ACh via the myenteric plexus was shown to act on a7nAChR on APCs.

What are examples of modulation of T-cells as a result of this?

Can inhibit Th17 response (key pro-inflammatory cell)

Can promote Treg response (key anti-inflammatory cell)

Which receptor is a 7 transmembrane protein coupled to a G protein? Nicotinic or Muscarinic?

Muscarinic receptor is a 7 transmembrane protein G protein coupled receptor

Which receptor is a Pentameric receptor? Nicotinic or Muscarinic?

Nicotinic receptor is a Pentameric receptor.

Are Muscarinic or Nicotinic receptors are able to promote immunosuppressive Treg cells and modulate B-cell function?

Nicotinic receptors.

How many Muscarinic receptors are present in humans?

5 total.

Expression of ACh receptors is homogenous and cells will either express muscarinic or nicotinic. 

True or False.

False.

Expression of ACh receptors is heterogenous. 

Expression of ACh receptors is dynamic and not constant. 

True or False?

True.

Expression is dynamic which suggests fine tuning of responses to ACh.

How does activation of a7nAChR cause suppression of NF-kB?

Activation causes inhibition of phosphorylation of NF-kB inhibitor (IkB)

• Prevents NF-kB release from its inhibitor (IkB)

• Inhibits activation as a result

How does activation of a7nAChR inhibit pro-inflammatory cytokine release

Activation also causes inhibition of TLR induced expression of pro-inflammatory cytokines 

Also activates JAK2 which activates STAT3 which can inhibit pro-inflammatory cytokine release 

Other muscarinic receptors are able to influence inflammation and cause anti-inflammatory effects not just a7nAChR.

True or False.

False.

While other muscarinic receptors are able to influence inflammation, not all of them cause anti-inflammatory effects. Some are pro-inflammatory