concanavalin-a and Gram-Negative-Bacterial-Infections

Th17 cells, a subset of T cells involved in autoimmunity and host defense against extracellular Gram-negative infection, express both IL-17A and IL-17F. Both IL-17A and IL-17F can signal via the IL-17RA; however, IL-17F does so at a 1- to 2-log higher concentration than IL-17A. In this study, we show that the IL-17F homodimer via IL-17RA is a negative regulator of IL-17 production in T cells and suggest a mechanism whereby IL-17RA on T cells serves as an autocrine/paracrine regulator of IL-17 synthesis in T cells.

Topics: Animals; Autocrine Communication; CD4-Positive T-Lymphocytes; Chemical and Drug Induced Liver Injury; Concanavalin A; Gram-Negative Bacterial Infections; Interleukin-17; Mice; Mice, Knockout; Mitogens; Paracrine Communication; Receptors, Interleukin-17; Signal Transduction

The interferon (IFN) gamma production of splenocytes from closely related C57BL/10ScSn (Sn) and C57BL/10ScCr (Cr) mice was compared. Concanavalin A and CD3 monoclonal antibodies induced high levels of IFN-gamma in both Sn and Cr splenocytes. By contrast, treatment with gram-negative bacteria induced IFN-gamma only in Sn splenocytes; in Cr splenocytes, the IFN-gamma response was heavily impaired. The IFN-gamma induction by bacteria requires the cooperation of IFN-gamma-producing cells with macrophages. Depletion of macrophages from Sn splenocytes resulted in the loss of ability to produce IFN-gamma after bacterial stimulation. Reconstitution with new Sn macrophages restored the IFN-gamma responsiveness, whereas reconstitution with Cr macrophages failed to do so. Normal function of IFN-gamma-producing cells and a defective function of macrophages of Cr mice was demonstrated by evidence showing that whole or macrophage-depleted Cr splenocytes, when supplemented with Sn macrophages, acquire the ability to produce IFN-gamma in response to bacteria. A similar effect was achieved by supplementing Cr splenocytes with supernatants of bacteria-stimulated Sn macrophages or with recombinant murine IFN-beta or IFN-alpha. Preincubation of active macrophage supernatants with antibodies to IFN-beta suppressed the helper activity for Cr splenocytes. Moreover, the bacteria-induced production of IFN-gamma by Sn splenocytes could be inhibited by antibodies to murine IFN-beta. The results provide evidence that IFN-beta is an important cofactor of IFN-gamma induction, which is not induced in Cr mice by gram-negative bacteria.

Topics: Animals; Base Sequence; CD3 Complex; Concanavalin A; Female; Gram-Negative Bacterial Infections; Interferon-beta; Interferon-gamma; Macrophages; Male; Mice; Mice, Inbred BALB C; Molecular Sequence Data