Mice model : Oral infection with Salmonella typhi
Has anyone tried infecting mice orally with Salmonella typhi (not S. typhimurium)? What was the result please? Specifically the invasion and the immune response (mucosal or systemic).
Thank you.
Not me but it has been done-basically as Typhi is restricted to humans (and perhaps other Great Apes) infection does not take. This is why Typhimurium (literally Mouse Typhoid) has been adopted as the model. This is not usually delivered orally either. Other restricted serovars (Gallinarum in the chicken for instance) lead to largely systemic Th1-dominated responses and avoid inflammatory responses at the gut. This is also considered the case for Typhi-where invasion is considered to be by 'stealth'.
So in brief don't waste your time trying as decades of research suggest it won't work.
I'm not...My work basically is kill the Salmonellas in meat and meat products.
It is human specific and doesn't do anything to mice , I know somebody did with Typhimurium,a few mice died .For Typhi you have to consider the human host !!
Mice will clear Typhi pretty quickly (basically poop them out). Typhi is not able to establish a systemic infection as it does in humans. It seems like Typhi needs certain components of the human immune response (co-evolution of Typhi and the human host). Typhi has a huge number of pseudogenes (non-functional or disrupted genes) compared with Typhimurium. In addition it has a capsule (the Vi capsule) that masks certain immune responses (like TLR-related response). There are a couple of humanized mouse models where they engrafted the human immune system and you can infect those with Typhi. These mouse strains are pretty expensive and you need special facilities. I use human cell cultures (primary monocyte derived macrophages and macrophage-like cells) for my Typhi infections. It seems like you want to look primarily at bacterial cell death/the ability of your treated bacteria to cause an infection (check if your treatment was successful and they are really dead)? How do you kill the Salmonella in the meat?
Azadeh Namvar and Paul Wigley.
do you have any reports or publications that can show ineffectiveness of typhi infection in mice?
Thanks.
Mr Jens Kortmann. It is pretty clear now. thanks.
I used an immuno-booster culture that I gave to mice. Now I want to challenge the immune system and I choosed salmonella for the same. the point was, typhi or typhimurium? In literature, nothing is said about typhi infection in mice model
Jens raises a number of good points-there are moves towards humanised mice and indeed bacterial Typhi:Typhimurium chimeras to study aspects of Typhoid in mice. For your study, assuming you wish to look at systemic protection, Typhimurium will do the job. If you wish to look at mucosal responses I would move out of Salmonella entirely and look at oral infection with Citrobacter rodentium. Salmonella does not cause enteritis in mice unless pre-treated with Streptomycin. As far as papers-these are going to be all 50 or more years old and not easy to access. Certainly Jens is in a good place to comment as Stanford has led much good research in thatarea through Stan Falkow and now Denise Monack.
I'm an avian specialist-they are much easier than mice for Salmonella!
Hey Tanedjeu, I agree with Paul. If you are primarily interested in challenging the immune system it might be nice to use a couple of different bacterial strains (as they might all help you answering different questions). In addition you would need Nramp positive mice to establish a chronic Salmonella infection (if you are interested in that).
Good luck with your experiments!
Jens
Hey Paul,
I am actually in Denise's lab at Stanford. I see a lot of differences when I compare human and murine cells in terms of adaptive immune responses/inflammasome activation. I have never looked into avian models. That sounds very interesting. Do you get chronic Salmonella carriers? Cheers!
Jens
Great-say 'Hi' to her for me. Basically the response to Typhimurium is an inflammatory one in the gut, but much more tightly regulated than mammals, so little damage or diarrhea but can lead to persistent gut carriage. The protective response in Th1 dominated.
Avian adapted serovars are more fun. There is a strong genetic element to resistance which is related to macrophages but largely independent of Nramp. Pullorum forms a systemic carrier state with recrudescent infection at point-of-laying. This is due to a natural decline in CD4 numbers-so less IFN-gamma. Not unlike what Denise showed in resistant mice after depleting IFN
S. Typhi is primarily a human pathogen so would not be a great idea to infect the mice orally with it. We can suspect that mice may not get infected!
I am 2 years too late to this conversation. However I would like to share this literature as evidence that Salmonella typhi is not mouse virulent by the oral route. If you inject IP with 5% gastric mucin though, the mouse will die, presumably by endotoxin shock.
Collins & Cater, 1978, Growth of salmonellae in orally infected germfree mice. Infect Immun, 21: 41-7.
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