Interactions between gut microbes and the immune system influence autoimmune disorders like systemic lupus erythematosus (SLE). Recently, Enterococcus gallinarum, a gram-positive commensal gut bacterium, was implicated as a candidate pathobiont in SLE. The present study was undertaken to evaluate the influence of E. gallinarum exposure on clinical parameters of SLE. Since circulating IgG antibodies to whole bacteria have been established as a surrogate marker for bacterial exposure, anti-E. gallinarum IgG antibodies were measured in banked serum samples from SLE patients and healthy controls in the Oklahoma Cohort for Rheumatic Diseases. The associations between anti-E. gallinarum antibody titers and clinical indicators of lupus were studied. Antibodies to human RNA were studied in a subset of patients. Our results show that sera from both patients and healthy controls had IgG and IgA antibodies reactive with E. gallinarum. The antibody titers between the two groups were not different. However, SLE patients with Ribosomal P autoantibodies had higher anti-E. gallinarum IgG titers compared to healthy controls. In addition to anti-Ribosomal P, higher anti-E. gallinarum titers were also significantly associated with the presence of anti-dsDNA and anti-Sm autoantibodies. In the subset of patients with anti-Ribosomal P and anti-dsDNA, the anti-E. gallinarum titers correlated significantly with antibodies to human RNA. Our data show that both healthy individuals and SLE patients were sero-reactive to E. gallinarum. In SLE patients, the immune response to E. gallinarum was associated with antibody response to a specific subset of lupus autoantigens. These findings provide additional evidence that E. gallinarum may be a pathobiont for SLE in susceptible individuals.

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The activation of the stimulator of interferon genes 1 (Sting1) pathway causes rapid induction of type I IFNs. Recently, different STING agonists are being proposed as therapeutics for controlling viral infections like those caused by the SARS-CoV-2. Considering that excessive STING activation leads to autoimmunity, this study was undertaken to investigate the effects of STING activation under pre-existing systemic inflammatory conditions induced by a viral infection. Female BALB/c mice were treated (Tx) with TLR3 agonist poly(IC), which was followed 24h later by subcutaneous injection of STING agonist diamidobenzimidazole (diAbZi). Only diAbZi or vehicle Tx mice were used as controls. Mice Tx with poly(IC) and diAbZi showed the highest systemic levels of type I IFNs, IL-6, and TNFα. Within 10 days, the salivary glands showed increased ILC1, monocytes, and CD8+ T cells. However, glandular function was not affected. Five days after Tx, except for the vehicle controls, all mice showed differing extents of redness, hair loss, and ulceration at the injection site. By day 10, diABZi alone Tx mice showed either normal skin or a small scar formation. In contrast, mice Tx with poly IC and diABZi, showed extensive hair loss, erythema, and ulceration. In addition, hematoxylin and eosin-stained skin sections showed extensive neutrophilic infiltration at the site of ulceration, epidermal thickening, and patchy lymphocytic infiltrate that extended into the subdermal layers. Our data demonstrate that STING activation under systemic inflammatory conditions, such as a viral infection, can lead to severe skin disease. Therefore, caution needs to be exercised in employing STING agonists as therapeutics for treating SARS-CoV-2.