Inhibition of murine splenic and mucosal lymphocyte function by enteric bacterial products.
Previously we showed that lysates of enteropathogenic Escherichia coli (EPEC) inhibit lymphokine production by mitogen-activated human peripheral blood and lamina propria mononuclear cells. The aims of the present study were to determine whether EPEC-inhibitory factors have similar effects on murine lymphoid populations in order to further delineate the mechanisms of alteration of cytokine production. Preexposure to EPEC lysates inhibited mitogen-stimulated interleukin-2 (IL-2), IL-4, and gamma interferon (IFN-gamma) production by murine spleen cells, but IL-10 production was increased. The inhibition was not due to increased apoptosis and was not blocked by neutralizating antibodies against IL-10 or transforming growth factor beta (TGF-beta). EPEC lysates also inhibited mitogen-stimulated IL-2 and IFN-gamma production by CD11b-depleted spleen cells, IL-2 and IL-4 production by intraepithelial and Peyer's patch lymphocytes, IL-2 production by the human T-cell line Jurkat, and antigen-stimulated IL-2 production by murine spleen cells. Lysates obtained from Shiga-like toxin-producing E. coli, E. coli RDEC-1, Citrobacter rodentium, and an EPEC espB insertion mutant all inhibited IL-2 and IL-4 production by mitogen-stimulated lymphoid cells. In conclusion, lysates of EPEC and related bacteria directly inhibit cytokine production by lymphoid cells from multiple sites by a mechanism that does not increase apoptosis or result from secondary effects of IL-10 or TGF-beta.
Malstrom
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Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA.
James
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D000818:Animals; D017209:Apoptosis; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D002954:Citrobacter / Q000472:pathogenicity*; D016207:Cytokines / Q000096:biosynthesis*; D004926:Escherichia coli / Q000472:pathogenicity*; D029968:Escherichia coli Proteins; D007413:Intestinal Mucosa / Q000276:immunology*; D008214:Lymphocytes / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology*
D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; C087863:EaeB protein, E coli; D029968:Escherichia coli Proteins; D016177:Macrophage-1 Antigen