Shanhao Jin

Fibroblasts exhibit phenotypic and functional heterogeneity in chronic inflammatory diseases, but how these changes impact immune outcomes remains poorly understood. We identified that a fibroblast population expressing insulin-like growth factor 1 (IGF1) was reduced in patients with inflammatory bowel disease (IBD). Using mouse models of intestinal inflammation, we found cross-talk between IGF1-expressing fibroblasts and group 3 innate lymphoid cells (ILC3s). IGF1 stimulation limited the ability of ILC3s to produce C-X-C motif chemokine ligand 10 (CXCL10) and recruit plasmacytoid dendritic cells (pDCs) to restrain gut inflammation. We propose that this regulatory pathway is conserved in human ILC3s but may become impaired in IBD. Our results define that anti-inflammatory fibroblasts safeguard the gut through regulation of an innate lymphocyte–pDC axis.

Background: Helicobacter hepaticus (H. hepaticus) has been demonstrated to have clinical relevance to the development of colitis in rodents. H. hepaticus produces cytolethal distending toxins (CDTs), which are identified as the most important virulence factors to the pathogenicity of CDT-producing bacteria in animals. However, the precise relationship between CDTs of H. hepaticus and intestinal barrier dysfunction remains unclear. The objective of the present study was to ascertain the impact of CdtB, the active subunit of CDTs, on the colonic mucosal barrier during H. hepaticus infection. Materials and Methods: We investigated the infection of male BALB/c mice, intestinal organoids, and IEC-6 cell monolayers by H. hepaticus or CdtB-deficient H. hepaticus (ΔCdtB). A comprehensive histopathological examination was conducted, encompassing the assessment of H. hepaticus colonization, the levels of mRNA expression for inflammatory cytokines, the expression levels of tight junction proteins, and the related signaling pathways. Results: The results demonstrate that the presence of ΔCdtB led to a mitigation of the symptoms associated with H. hepaticus-induced colitis, as evidenced by colon length shortening and the colon histological inflammation score. In addition, the levels of pro-inflammatory cytokines were reduced in the ΔCdtB group. Moreover, a downward trend was observed in the phosphorylation levels of STAT3 and nuclear factor-κB (p65). In vitro, the presence of H. hepaticus resulted in a reduction in the expression of tight junction (TJ) markers (ZO-1 and occludin) and an impairment of the F-actin structure in either the intestinal epithelium or intestinal organoids. However, these effects were reversed by CdtB deletion. Concurrently, both ROS levels and apoptosis levels were found to be significantly reduced in cells treated with the ΔCdtB strain. Mechanistically, myosin light chain kinase (MLCK) activation was observed in the H. hepaticus-infected group in vivo, whereas the MLCK inhibitor ML-7 was found to reverse the CdtB-induced alterations in TJ proteins in IEC6 cells. Conclusions: The collective findings demonstrate that CdtB plays a pivotal role in the H. hepaticus-induced colonic mucosal barrier. This is achieved through the regulation of TJs via the MLCK/pMLC2 signaling pathway, which is linked to elevations in oxidative stress and inflammation within intestinal epithelial cells.

Keeping chickens as backyard pets has become increasingly popular in the United States in recent years. However, biosecurity is generally low in backyard flocks. As a consequence, they can serve as reservoirs for various pathogens that pose a risk for commercial poultry or human health. Eighty-four fecal samples, 82 from chickens and two from turkeys, from 64 backyard flocks throughout the state of Alabama were collected in the summers of 2017 and 2018. Coccidia oocysts were seen in 64.1% of flocks with oocyst counts in most samples below 10,000 oocysts per gram. Eggs of Ascaridia spp. or Heterakis gallinarum were observed in 20.3% of the flocks, and eggs of Capillaria spp. in 26.6% of the flocks. Egg counts were low, rarely exceeding 1000 eggs per gram. DNA extracted directly from fecal samples was investigated by PCR for other relevant parasites. The results showed that 4.7% of flocks were positive for Histomonas meleagridis, 18.8% of flocks for Tetratrichomonas gallinarum, 18.8% of flocks for Cryptosporidium spp. and 87.5% of flocks for Blastocystis spp. The results will help to provide information that can be used to design outreach programs to improve health and wellbeing of birds in backyard flocks.