1. Pericytes modulate endothelial inflammatory response during bacterial infection
- Author
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Carvalho, Thaynara P, Toledo, Frank AO, Bautista, Diego FA, Silva, Monique F, Oliveira, Jefferson BS, Lima, Pâmela A, Costa, Fabíola B, Ribeiro, Noelly Q, Lee, Jee-Yon, Birbrair, Alexander, Paixão, Tatiane A, Tsolis, Reneé M, and Santos, Renato L
- Subjects
Microbiology ,Biological Sciences ,Biomedical and Clinical Sciences ,Digestive Diseases ,Biodefense ,Infectious Diseases ,Emerging Infectious Diseases ,2.1 Biological and endogenous factors ,Animals ,Mice ,Sheep ,Pericytes ,Endothelial Cells ,Connexin 43 ,Inflammation ,Bacterial Infections ,inflammation ,pericytes ,endothelial cells ,connexin 43 ,Brucella ,Listeria ,Citrobacter ,Biochemistry and cell biology ,Medical microbiology - Abstract
Pericytes are located around blood vessels, in close contact with endothelial cells. We discovered that pericytes dampen pro-inflammatory endothelial cell responses. Endothelial cells co-cultured with pericytes had markedly reduced expression of adhesion molecules (PECAM-1 and ICAM-1) and proinflammatory cytokines (CCL-2 and IL-6) in response to bacterial stimuli (Brucella ovis, Listeria monocytogenes, or Escherichia coli lipopolysaccharide). Pericyte-depleted mice intraperitoneally inoculated with either B. ovis, a stealthy pathogen that does not trigger detectable inflammation, or Listeria monocytogenes, developed peritonitis. Further, during Citrobacter rodentium infection, pericyte-depleted mice developed severe intestinal inflammation, which was not evident in control mice. The anti-inflammatory effect of pericytes required connexin 43, as either chemical inhibition or silencing of connexin 43 abrogated pericyte-mediated suppression of endothelial inflammatory responses. Our results define a mechanism by which pericytes modulate inflammation during infection, which shifts our understanding of pericyte biology: from a structural cell to a pro-active player in modulating inflammation.ImportanceA previously unknown mechanism by which pericytes modulate inflammation was discovered. The absence of pericytes or blocking interaction between pericytes and endothelium through connexin 43 results in stronger inflammation, which shifts our understanding of pericyte biology, from a structural cell to a player in controlling inflammation.
- Published
- 2024