Lipopolysaccharide or whole bacteria block the conversion of inflammatory monocytes into dendritic cells in vivo.
Monocytes can develop into dendritic cells (DCs) that migrate to lymph nodes (LNs) and present antigens to T cells. However, we find that this differentiation is blocked when monocytes accumulate subcutaneously in response to bacteria or lipopolysaccharide (LPS). The inhibition of DC differentiation is mediated by the bacteria and in conjunction with inflammatory cells recruited at the site of injection. Inhibition of migratory DC development was reversed in Toll-like receptor (TLR)4-mutated mice when LPS, but not whole bacteria, was injected, suggesting that TLR4 is one but not the only mediator of the inhibition. The block imposed by bacteria was partly relieved by the absence of interleukin (IL)-12 p40, but not by individual absence of several cytokines involved in DC differentiation or in inflammation, i.e., IL-6, IL-10, IL-12 p35, and interferon gamma. Consistent with the inability of monocytes to yield migrating DCs, and the finding that other DCs had limited access to particulate or bacterial antigens, these antigens were weakly presented to T cells in the draining LN. These results illustrate that bacteria-associated signals can have a negative regulatory role on adaptive immunity and that local innate responses for containment of infectious bacteria can at least initially supersede development of adaptive responses.
Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti, 435, 20141 Milano, Italy.
Gianluca
G
Rotta
Emmerson W
EW
Edwards
Sabina
S
Sangaletti
Clare
C
Bennett
Simona
S
Ronzoni
Mario P
MP
Colombo
Ralph M
RM
Steinman
Gwendalyn J
GJ
Randolph
Maria
M
Rescigno
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors