No abstract

Bacterial translocation is associated with clinically relevant complications in cirrhosis. We evaluated the effect of toll-like receptor polymorphisms in the soluble response against these episodes. Consecutive patients with cirrhosis and ascitic fluid were distributed by TLR2 rs4696480, TLR4 rs4986790, and TLR9 rs187084 single-nucleotide polymorphisms. Lipoteichoic acid, lipopolyssaccharide, bacterial-DNA, pro-inflammatory cytokines and nitric oxide levels were quantified in serum samples. In vitro response against specific ligands in variant TLR genotypes was evaluated. One hundred and fourteen patients were included. Variant TLR-2, TLR-4 and TLR-9 SNP genotypes were associated with significantly increased serum levels of LTA, LPS and bacterial-DNA. TNF-α, IL-6 and nitric oxide serum levels were significantly decreased in all variant TLR genotyped patients. Cytokine levels were significantly less upregulated in response to specific TLR-ligands in patients with all variant vs wildtype TLR genotypes. Although in vitro gene expression levels of all wildtype and variant TLRs were similar, MyD88 and NFkB were significantly downregulated in cells from TLR-variant genotyped patients in response to their ligands. Variant TLR genotypes are associated with an increased circulating antigen burden and a decreased proinflammatory response in cirrhosis. This immunodeficiency may facilitate bacteria-related complications in cirrhosis and enhance TLR targeting for its management.

These results provide a plausible mechanism for the immunomodulatory effects of norfloxacin in cirrhosis beyond its bactericidal effect.

SARS-CoV-2 is the virus that causes the disease called COVID-19, which has caused the worst pandemic of the century. Both, to know the immunological status of general population and to evaluate the efficacy of the vaccination process that is taking place around the world, serological tests represent a key tool. Classic serological tests, based on colorimetric techniques, such as ELISA or CLIA, continue to be the most widely used option. However, a real improvement in results is still needed. We developed a highly sensitive and specific FCM assay that allows the detection of IgG and IgA antibodies, directed against the native and functional S-protein of SARS-CoV-2 exposed on the membrane of a transfected cell line, up to 8 months after infection.

Intestinal permeability to translocation of bacterial products is increased in cirrhosis. Regulatory T cells (Tregs) remain central to the interplay between the host and microbial milieu. We propose that Tregs are involved in promoting gut barrier integrity and a balanced interaction with gut microbiota–derived short‐chain fatty acids (SCFAs). Carbon tetrachloride cirrhosis was induced in wild‐type and recombination activating gene 1 (Rag1)‐/‐ mice. Naive T cells and Treg cells were transferred into Rag1 ‐/‐ mice. Intestinal permeability was assessed in vivo after lipopolysaccharide (LPS) oral administration, and bacterial DNA presence was evaluated in mesenteric lymph nodes. Transcript and protein levels of tight‐junction (TJ) proteins were measured in colonic tissue. Intestinal T helper profile in response to Escherichia coli (E. coli) was determined by flow cytometry. SCFAs were measured by gas chromatography–mass spectrometry in colonic content before and after E. coli challenge. Rag1 ‐/‐ mice showed significantly increased permeability to LPS and bacterial DNA translocation rate compared with control mice. Naive T and Treg cotransfer significantly reduced gut permeability to bacterial antigen translocation and restored TJ protein expression in Rag1 ‐/‐ mice. Naive T and Treg replenishment in Rag1 ‐/‐ mice restrained proinflammatory differentiation of intestinal lymphocytes in response to E. coli. The main SCFA concentration resulted in significant reduction in Rag1 ‐/‐ mice after E. coli administration but remained unaltered after naive T and Tregs cotransfer. The reduced expression of SCFA receptors induced by E. coli was reestablished following naive T and Treg reconstitution in Rag1 ‐/‐ mice. Conclusion: The restriction of gut permeability, local inflammatory differentiation, and loss of bacteria‐derived SCFAs foster the value of Tregs in preventing bacterial translocation in cirrhosis.