B-1 cells temper endotoxemic inflammatory responses.
Sepsis syndrome is caused by inappropriate immune activation due to bacteria and bacterial components released during infection. This syndrome is the leading cause of death in intensive care units. Specialized B-lymphocytes located in the peritoneal and pleural cavities are known as B-1 cells. These cells produce IgM and IL-10, both of which are potent regulators of cell-mediated immunity. It has been suggested that B-1 cells modulate the systemic inflammatory response in sepsis. In this study, we conducted in vitro and in vivo experiments in order to investigate a putative role of B-1 cells in a murine model of LPS-induced sepsis. Macrophages and B-1 cells were studied in monocultures and in co-cultures. The B-1 cells produced the anti-inflammatory cytokine IL-10 in response to LPS. In the B-1 cell-macrophage co-cultures, production of proinflammatory mediators (TNF-α, IL-6 and nitrite) was lower than in the macrophage monocultures, whereas that of IL-10 was higher in the co-cultures. Co-culture of B-1 IL-10(-/-) cells and macrophages did not reduce the production of the proinflammatory mediators (TNF-α, IL-6 and nitrite). After LPS injection, the mortality rate was higher among Balb/Xid mice, which are B-1 cell deficient, than among wild-type mice (65.0% vs. 0.0%). The Balb/Xid mice also presented a proinflammatory profile of TNF-α, IL-6 and nitrite, as well as lower levels of IL-10. In the early phase of LPS stimulation, B-1 cells modulate the macrophage inflammatory response, and the main molecular pathway of that modulation is based on IL-10-mediated intracellular signaling.
Barbeiro
Denise Frediani
DF
Clinical Laboratory in Emergency Medicine, University of São Paulo, School of Medicine, São Paulo, Brazil. denisedna@hotmail.com
Barbeiro
Hermes Vieira
HV
Faintuch
Joel
J
Ariga
Suely K Kubo
SK
Mariano
Mario
M
Popi
Ana Flávia
AF
de Souza
Heraldo Possolo
HP
Velasco
Irineu Tadeu
IT
Soriano
Francisco Garcia
FG
D000818:Animals; D030801:Animals, Genetically Modified; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D018920:Coculture Techniques; D019446:Endotoxemia / Q000276:immunology*; D055786:Gene Knockout Techniques; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009573:Nitrites / Q000276:immunology; D010529:Peritoneal Cavity; D035422:Pleural Cavity / Q000276:immunology; D018805:Sepsis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D015850:Interleukin-6; D008070:Lipopolysaccharides; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10