Reactive arthritis, an autoimmune disorder, occurs following gastrointestinal infection with invasive enteric pathogens, such as Salmonella enterica. Curli, an extracellular, bacterial amyloid with cross beta-sheet structure can trigger inflammatory responses by stimulating pattern recognition receptors. Here we show that S. Typhimurium produces curli amyloids in the cecum and colon of mice after natural oral infection, in both acute and chronic infection models. Production of curli was associated with an increase in anti-dsDNA autoantibodies and joint inflammation in infected mice. The negative impacts on the host appeared to be dependent on invasive systemic exposure of curli to immune cells. We hypothesize that in vivo synthesis of curli contributes to known complications of enteric infections and suggest that cross-seeding interactions can occur between pathogen-produced amyloids and amyloidogenic proteins of the host. Our manuscript focuses on curli, a ‘functional amyloid’ produced by Salmonella as well as other enteric bacteria. We present the first biochemical evidence that these fibers are produced in the gastrointestinal tract of mice after oral infection, the natural route for Salmonella infections. This finding is significant because of the immune impacts on the host; we show that curli cause an increase in autoimmunity and inflammation in the knee joints of infected mice. Reactive arthritis is a known autoimmune complication after enteric infections and our results indicate that presence of curli in the gut provides a novel linchpin of pathogenesis. As curli or curli-like amyloids are also produced by the commensal bacteria, it is possible that the unintended release of amyloids produced by the microbiota could trigger similar autoimmune reactions. Finally, our work provides conceptual evidence for the possibility of cross-seeding between bacterial amyloids like curli and human amyloids involved in amyloid-associated diseases such as Alzheimer’s Disease via the gut microbiome or infections.

Oral progestagen treatment extends the weaning-to-estrus interval (WEI) in weaned sows. Particularly in lower parity sows, this allows recovery from lactational catabolism and improves sow productivity. However, the optimal duration of progestagen treatment in contemporary dam-line sows is unclear. Therefore, sows (n = 749) weaned over consecutive 3-wk periods in June and July and classified as parity 2 and 3 (P2–3); 4, 5, and 6 (P4–6); or parity 7 or higher (P7+) were organized into 2 breeding groups using 1 of 3 strategies: 1) oral progestagen for 2 d before and 12 d after weaning (M14; n = 249); 2) oral progestagen for 2 d before and 5 d after weaning (M7; n = 250); or 3) no progestagen treatment (M0; n = 250). Progestagen (altrenogest) was administered directly into the sow's mouth at a dosage of 6.8 mL (15 mg of altrenogest) daily. Sows were bred using artificial insemination at first detection of estrus after weaning (M0) or altrenogest withdrawal, and every 24 h thereafter, until they no longer exhibited the standing reflex. The WEI for M0 sows was 5.1 ± 0.1 d. Estrus was recorded sooner (P < 0.001) after withdrawing treatment in M14 than in M7 sows (6.9 ± 0.1 vs. 7.4 ± 0.1 d, respectively). More (P < 0.001) M14 sows (88.6 ± 2.5%) were bred within 10 d of altrenogest withdrawal than M7 (72.8 ± 2.8%) sows, or within 10 d of weaning in M0 sows (78.8 ± 2.6%). Reproductive tracts were recovered after slaughter at d 30 or 50 of gestation. For P2–3 sows, ovulation rate (least squares mean ± 95% confidence interval) in M7 (23.1 ± 1.0) was greater (P < 0.001) than in M14 (20.7 ± 1.0) or M0 (19.7 ± 1.0) sows; no differences were detected in P4–6 and P7+ sows. At d 30, M7 and M14 sows had more (P < 0.01) embryos (16.4 ± 0.6 and 15.8 ± 0.4, respectively) than M0 (13.9 ± 0.5) sows. At d 50 of gestation, number of fetuses in M14 sows (13.6 ± 0.4) was greater (P < 0.001) than in M0 (11.8 ± 0.4) and M7 (12.2 ± 0.3) sows. Use of oral progestagen to delay the return to postweaning estrus for greater than 18 d appears to have potential for improving weaned sow productivity. Given the incidence of high ovulation rates and associated evidence of intrauterine crowding of embryos around d 30 of gestation, the changing dynamics of prenatal loss resulting from longer periods of progestagen treatment may represent an additional production advantage.

Newborn piglets are immunologically naïve and must receive passive immunity via colostrum within 24 hours to survive. Mechanisms by which the newborn piglet gut facilitates uptake of colostral cells, antibodies, and proteins may include FcRn and pIgR receptor‐mediated endocytosis and paracellular transport between tight junctions (TJs). In the present study, FcRn gene (FCGRT) was minimally expressed in 6‐week‐old gut and newborn jejunum but it was expressed at significantly higher levels in the ileum of newborn piglets. pIgR was highly expressed in the jejunum and ileum of 6‐week‐old animals but only minimally in neonatal gut. Immunohistochemical analysis showed that Claudin‐5 localized to blood vessel endothelial cells. Claudin‐4 was strongly localized to the apical aspect of jejunal epithelial cells for the first 2 days of life after which it was redistributed to the lateral surface between adjacent enterocytes. Claudin‐4 was localized to ileal lateral surfaces within 24 hours after birth indicating regional and temporal differences. Tissue from gnotobiotic piglets showed that commensal microbiota did not influence Claudin‐4 surface localization on jejunal or ileal enterocytes. Regulation of TJs by Claudin‐4 surface localization requires further investigation. Understanding the factors that regulate gut barrier maturation may yield protective strategies against infectious diseases.