Both beneficial and pathogenic organism might have similar MAMP ( microorganism associated molecular pattern) such as flagellin,LPS dsRNA.CpG etc .HOW do our Host cell TLR(Toll like receptor) can discriminate pathogen and beneficial microorganism with the MAMP .that are invaded into human host and decide to elicit immune response only against pathogen but not against beneficial micro organism.. .
The anatomical location of the pathogen vs commensal is usually different. Commensals line the epithelial barrier and remain associated with the tight mucus layer lining the epithelial cells, whereas pathogens will penetrate the barrier and enter the lumen. Additionally, commensals will secrete or produce compounds (eg. metabolites like butyrate etc), which can induce an immunosuppressive environment (induction of Tregs, myeloid derived suppressor cells etc) such that immune system cannot kill commensals. It is still not very clear if there are differences in innate recognition of commensal v pathogen but this is an active area of investigation!
The anatomical location of the pathogen vs commensal is usually different. Commensals line the epithelial barrier and remain associated with the tight mucus layer lining the epithelial cells, whereas pathogens will penetrate the barrier and enter the lumen. Additionally, commensals will secrete or produce compounds (eg. metabolites like butyrate etc), which can induce an immunosuppressive environment (induction of Tregs, myeloid derived suppressor cells etc) such that immune system cannot kill commensals. It is still not very clear if there are differences in innate recognition of commensal v pathogen but this is an active area of investigation!
Is there a cost associated with secretion of these compounds? Otherwise, why haven't pathogenic microorganisms evolved to do the same? Just curious.
Also, we have to take into account the need of association of several PRRs to gain appropriate response. According to the associated sensors (PRRs), the response should be either beneficial or deleterious for the commensal/pathogen and/or the host
some think that pathogens are so because the "failed" to be commensals. Read article by Locksley :commensalism gone awry" or a similar title. Others consider pathogens and commensals to be the same, they are microorganisms. In my hands the dose is critical, a "good" bacteria can often be harmful if it is present at high enough doses. This is due to the balance between anti and pro inflammatory cytokines. A good symbiont is often very good at inducing TGFb but not a pathogen. The Vibrio fisheri/squid story is a great way to look at this in a simplistic manner. My answer is also just a part of a very long intricate
answer
I suggest you the following articles.
Kelly D, Mulder IK. Microbiome and immunological interactions. Nutrition Reviews. 2012; 70 (Suppl. 1): S18–S30.
Swiatczak B, Rescigno M c, Cohen IR. Systemic features of immune recognition in the gut. Microbes and Infection. 2011; 13: 983-991.
Schulz O, Pabst O. Antigen sampling in the small intestine. Trends in Immunology. 2013; 34 (4): 155-161.
A lot of it has also to do where your commensals show up. I.e. TLR5 is only expressed at the bass-lateral side of cells in the intestine, which would mean that if you detect bacteria there, there is a damage to the tissue. So, every commensal that shows up at the wrong time at the wrong place, it can be a pathogen. In addition, you have many cells that constantly sample the environment, but APC alone are not enough to induce a full blown response.There are Tregs etc ensuring a constant "state of anergy" - maybe thats the norm. We also know that there are subtle differences in the sugars compositions, meaning that, if you take host-pathogen evolution into account, the TLRs may have a lower threshold level to a PAMP than to a MAMP. And there are additional receptors (all he C-type lectin R, the MR etc) - so I guess the sum of all activation, and how a signal is multiplied i.c. (NFkB only, or MAPK activation as well etc) may make the final signal
One clear explanation that i read is Gewirtz et al., 2001 .Reported that TLR5 is expressed on the basolateral surface ,but not the apical side of intestinal epithelial cels.suggesting that flagellin is detected when bateria invade across the epithelium .
From this can we can tell that Beneficail micro organism will reside in mucosal surface so it is not detected by TLR5 ,thus there is no inflammation or immune reaction ..
Kindly do provide me some MORE info HOW do our Host cell TLR can discriminate pathogen and beneficial microorganism that are invaded in human host ..
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