NZWxBXSB F1 will eventually succumb to disease even after anti-E. Gall treatment (but much later).
Another factor could be intra-host evolution (pubmed.ncbi.nlm.nih.gov/35831502/)

There is probably still a genetic (?) component that determines if someone develops the full disease. There are studies detecting E.gall in ~5-10% of the population (luckily autoimmunity is rarer) . We also saw that "normal" B6 mice will recover after stopping IMQ induction of pathology,.. while

..where it leads to B cell maturation and autoantibody production. We observe a strong correlation between anti-E.gall antibodies and autoantibodies of the IgG3 subclass in SLE patients. To conclude with Hippocrates: all disease starts in the gut!

To summarize: We characterize E.gall as one of the few confirmed human pathobionts that can induce extraintestinal Th17 immunity. The mechanism involves TLR8 activation in APCs and CD86 induction. E.gall has the ability to translocate to systemic sites,..

To put it all to a mechanistic test, we transferred E.gall into B6-SPF mice and used IMQ to induce an SLE-like pathology. The presence of E.gall aggravated proteinuria and lead to IgG3 deposits in the kidney

We saw that IgG3-reactivities against human autoantigens and E.gall RNA strongly correlated with each other, while anti-E.coli RNA antibodies did not. We confirmed this in another independent patient cohort. We also observed that the strongest reactivity was seen in patients with more severe disease

Next we looked at autoantibodies from patients with SLE or AIH. All patients with SLE had antibodies targeting E.gall RNA, while there was no increase in anti-E.coli RNA antibodies compared to healthy donors. Next we looked at IgG subclasses.

Interestingly, blocking lysosome activity via hydroxychloroquine - a drug commonly used as medication in SLE - had a comparable effect. RNA is considered an autoantigen in SLE, suprisingly E.gall-RNA was much more potent in IFNa induction compared to human RNA.

What part of E.gall is activating the APCs? Destruction of proteins or cell wall did not have any effect, but blockade of the RNA-sensor TLR8 abrogates all Th17 inducing activity of E.gall. But to reach TLR8, bacteria need to be inside the APC - and indeed we could observe live E.gall in monocytes.

And mechanistically? It only works if you have antigen-presenting cells present. E.gall specifically induced CD86, and blockade of CD86, but not CD80, prevents Th17 induction. Emphasizing that CD80 and CD86 are distinct! We also see a TCR activation and expansion of cytokine producing T cell clones.

What's so special about E.gall? We saw that it can move through the intestinal wall and was the only bacterium that bypassed the firewall Organs (MLN, Liver) and ended up in the spleen, where it induced B cell maturation and autoantibody production.

We now wondered how exactly E.gall would induce Th17 immunity and if this would also work in humans. We observed that E.gall is a potent inducer of human Th17 cells. Surprisingly, also other Enterococci were able to do so.

We previously identified the intestinal pathobiont Enterococcus gallinarum in autoimmune-prone mice and in tissue biopsies from patients with systemic lupus erythematosus (SLE) or autoimmune hepatitis (AIH). E.gall induced Th17 Responses in mice, and its eradication ameliorated SLE-like pathology.