RESUMO
The omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs) that collects peritoneal contaminants and provides a first layer of immunological defense within the abdomen. Here, we investigated the mechanisms that mediate the capture of peritoneal contaminants during peritonitis. Single-cell RNA sequencing and spatial analysis of omental stromal cells revealed that the surface of FALCs were covered by CXCL1+ mesothelial cells, which we termed FALC cover cells. Blockade of CXCL1 inhibited the recruitment and aggregation of neutrophils at FALCs during zymosan-induced peritonitis. Inhibition of protein arginine deiminase 4, an enzyme important for the release of neutrophil extracellular traps, abolished neutrophil aggregation and the capture of peritoneal contaminants by omental FALCs. Analysis of omental samples from patients with acute appendicitis confirmed neutrophil recruitment and bacterial capture at FALCs. Thus, specialized omental mesothelial cells coordinate the recruitment and aggregation of neutrophils to capture peritoneal contaminants.
Assuntos
Apendicite/imunologia , Linfócitos/imunologia , Neutrófilos/imunologia , Omento/imunologia , Peritonite/imunologia , Células Estromais/imunologia , Doença Aguda , Animais , Apendicite/genética , Apendicite/microbiologia , Comunicação Celular/imunologia , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Epitélio/imunologia , Epitélio/microbiologia , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/patogenicidade , Armadilhas Extracelulares/imunologia , Feminino , Expressão Gênica , Humanos , Linfócitos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos , Neutrófilos/microbiologia , Omento/microbiologia , Peritonite/induzido quimicamente , Peritonite/genética , Peritonite/microbiologia , Proteína-Arginina Desiminase do Tipo 4/genética , Proteína-Arginina Desiminase do Tipo 4/imunologia , Análise de Sequência de RNA , Análise de Célula Única , Células Estromais/microbiologia , Técnicas de Cultura de Tecidos , Zimosan/administração & dosagemRESUMO
ILC2s were originally identified as IL-5 and IL-13 secreting "natural helper cells" present within the fat-associated lymphoid clusters of the mesenteries in both mouse and man. The presence of ILCs in adipose tissue has more recently expanded to include all ILC groups. Since their initial discovery, our knowledge of these cells and their role in adipose immune responses has expanded significantly. In this review we summarize the current literature on the role that ILC2s play in orchestrating adipose tissue function in both lean and obese states. We go on to address new data detailing interactions of adipose ILCs with innate like B-cells (IBC) and discuss how this interaction results in localized protection of mucosal sites during infection and inflammation via the production of innate antibodies.
