Interleukin‐10 Produced by the Innate Immune System Masks In Vitro Evidence of Acquired T‐Cell Immunity to E. coli

Abstract

Hessle C, Hanson LA Ê , Wold AE. Interleukin-10 Produced by the Innate Immune System Masks In Vitro Ecidence of Acquired T-Cell Immunity. Scand J Immunol 2000;52:13±20 Bacteria trigger stimulation of antigen-speci®c, as well as innate, immune responses. Cytokines and other products of cells belonging to the innate immune system may interfere with the detection of acquired immunity to whole bacteria in vitro. Proliferation and cytokine production by human blood mononuclear cells in response to a whole UV-killed Escherichia coli was compared with the response to commonly used antigen preparations: puri®ed protein derivative (PPD), Candida albicans and in¯uenza proteins. E. coli induced a weaker proliferative response with later onset than did the other antigens, and production of interferon (IFN)-g comparable with that in response to C. albicans and in¯uenza vaccine, but lower than that induced by PPD. Both proliferation and IFN-g production were abolished by removal of CD4 cells or blocking of HLA-D, but not CD1 antigen-presenting molecules. Puri®ed lipopolysaccharide (LPS) induced neither proliferation nor IFN-g production. None of the antigen preparations stimulated interleukin (IL)-4 production but, in contrast to the other antigens, whole E. coli, as well as puri®ed O6 LPS, induced large quantities of IL-10. IL-10 production was independent of CD4 cells or HLA-D molecules. Blocking of IL-10 by neutralizing antibodies increased both E. coli-induced proliferation and IFN-g production markedly. Conversely, the addition of whole E. coli or LPS to cultures stimulated with other antigens (C. albicans or Staphylococcus aureus) downregulated proliferative and IFN-g responses, an effect which was at least partly IL-10 dependent. The results indicate a substantial T-cell memory to commensal E. coli, but suggest that the evidence of such memory, e.g. proliferation and IFN-g production, is effectively prevented by IL-10 and perhaps other factors produced by monocytes in response to bacteria. Thus, the innate immune responses must be taken into account when acquired immune responses to microbes are measured.

Monocyte-Derived Interleukin-10 Depresses the Bordetella pertussis - Specific Gamma Interferon Response in Vaccinated Infants

“…However, whereas the polymorphism may be linked to IL-10 secretion at 2 months, this was not the case at 6 months, suggesting that other factors, including nongenetic factors, trigger this IL-10 secretion by the monocytes at 6 months. Commensal bacteria from the intestinal microflora, such as Escherichia coli, have been reported to induce the secretion of IL-10 by human monocytes, leading to low acquired T-cell-mediated immunity (8,9). Similarly, some bacterial virulence factors, such as FHA, included in most acellular vaccines against pertussis, have been shown to induce IL-10 production and to inhibit IL-12 secretion by a macrophage cell line via an IL-10-dependent mechanism (17,21).…”

“…Acquired immune responses are generally modulated by responses from the innate immune system, and specific IFN-␥ responses are often modulated by IL-10. This prototypical regulatory cytokine, produced by monocytes and dendritic cells, as well as by T lymphocytes, has been shown to dampen the specific T-cell responses to several pathogens (8,17,20). Interindividual variations in IL-10 production can be a consequence of a genetic polymorphism (5,25,26), as well as numerous other factors (8,9,17,21).…”

Characterization of Humoral and Cellular Immune Responses Elicited by Meningococcal Carriage

“…Pollard et al (33) described that high levels of IL-10 were secreted by PBMCs, collected from convalescent patients and healthy adults, in response to stimulation with meningococcal outer membrane vesicles. IL-10 produced by monocytes during the incubation of PBMCs with LPS or Escherichia coli cells has been reported to result in the inhibition of cellular proliferation (18). It seems likely that such a mechanism could have inhibited the meningococcusspecific proliferation assays.…”

Polymorphisms in lymphotoxin alpha and CD14 genes influence TNFα production induced by Gram-positive and Gram-negative bacteria

“…Bacteria were grown to late logarithmic phase growth, washed two times with warm PBS and killed by incubation at 651C for 20 min as described. 24 Bacteria were counted in a haemocytometer and killing was confirmed by cultivation on horse blood agar. Bacteria were stored at À801C in 20% glycerol/80% PBS.…”