title: Absence of platelet endothelial cell adhesion molecule 1, PECAM-1/CD31, in vivo increases resistance to Salmonella enterica serovar Typhimurium in mice.
abstract: PECAM-1/CD31 is known to regulate inflammatory responses and exhibit pro- and anti-inflammatory functions. This study was designed to determine the functional role of PECAM-1 in susceptibility to murine primary in vivo infection with Salmonella enterica serovar Typhimurium and in in vitro inflammatory responses of peritoneal macrophages. Lectin profiling showed that cellular PECAM-1 and recombinant human PECAM-1-Ig chimera contain high levels of mannose sugars and N-acetylglucosamine. Consistent with this carbohydrate pattern, both recombinant human and murine PECAM-1-Ig chimeras were shown to bind S. Typhimurium in a dose-dependent manner in vitro. Using oral and fecal-oral transmission models of S. Typhimurium SL1344 infection, PECAM-1(-/-) mice were found to be more resistant to S. Typhimurium infection than wild-type (WT) C57BL/6 mice. While fecal shedding of S. Typhimurium was comparable in wild-type and PECAM-1(-/-) mice, the PECAM-1-deficient mice had lower bacterial loads in systemic organs such as liver, spleen, and mesenteric lymph nodes than WT mice, suggesting that extraintestinal dissemination was reduced in the absence of PECAM-1. This reduced bacterial load correlated with reduced tumor necrosis factor (TNF), interleukin-6 (IL-6), and monocyte chemoattractant protein (MCP) levels in sera of PECAM-1(-/-) mice. Following in vitro stimulation of macrophages with either whole S. Typhimurium, lipopolysaccharide (LPS) (Toll-like receptor 4 [TLR4] ligand), or poly(I·C) (TLR3 ligand), production of TNF and IL-6 by PECAM-1(-/-) macrophages was reduced. Together, these results suggest that PECAM-1 may have multiple functions in resistance to infection with S. Typhimurium, including binding to host cells, extraintestinal spread to deeper tissues, and regulation of inflammatory cytokine production by infected macrophages.
authors.affiliation: Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lovelace
authors.forename: May Lin
authors.initials: ML
authors.lastname: Yap
authors.forename: Jana
authors.initials: J
authors.lastname: Yip
authors.forename: William
authors.initials: W
authors.lastname: Muller
authors.forename: Odilia
authors.initials: O
authors.lastname: Wijburg
authors.forename: Denise E
authors.initials: DE
authors.lastname: Jackson
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D017737:Macrophages, Peritoneal; D051379:Mice; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000276:immunology / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D059467:Transcriptome
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins