Monocytes/macrophages and/or neutrophils are the target of IL-10 in the LPS endotoxemia model.
IL-10 is a potent regulator of the innate and adaptive immune responses. Several cell types produce IL-10 and its receptor chains and these may regulate different immune responses. Here we report that inactivation of the IL-10 receptor (IL-10R1) gene in mice leads to an increased susceptibility to chemically induced colitis as in the classical IL-10-deficient mutant. To identify the cells regulated by IL-10 in immune responses, we generated several cell type specific IL-10R1-deficient mutants. We show that, in an IL-10-dependent LPS model of endotoxemia, dampening of the immune response requires expression of IL-10R1 in monocytes/macrophages and/or neutrophils but not in T cells nor B cells. As the macrophage and/or neutrophil-specific IL-10-deficient mutants also display the same phenotype, our results suggest that an autocrine loop in monocytes/macrophages is the most probable mechanism for the regulation of an LPS-induced septic shock. In contrast, in an IL-10-regulated T-cell response to Trichuris muris infection, IL-10 acting on T cells or monocytes/macrophages/neutrophils is not critical for the control of the infection.
Pils
Marina C
MC
Department of Experimental Immunology, Helmholtz-Centre for Infection Research, Braunschweig, Germany. marina.pils@helmholtz-hzi.de
Pisano
Fabio
F
Fasnacht
Nicolas
N
Heinrich
Jan-Michael
JM
Groebe
Lothar
L
Schippers
Angela
A
Rozell
Björn
B
Jack
Robert S
RS
Müller
Werner
W
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002432:Cecum / Q000469:parasitology / Q000473:pathology; D019446:Endotoxemia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D005260:Female; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D053701:Receptors, Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014257:Trichuriasis / Q000276:immunology / Q000469:parasitology; D014258:Trichuris / Q000254:growth & development / Q000276:immunology
D008070:Lipopolysaccharides; D053701:Receptors, Interleukin-10; D016753:Interleukin-10