Intracellular Salmonella dublin induces substantial secretion of the 40-kilodalton subunit of interleukin-12 (IL-12) but minimal secretion of IL-12 as a 70-kilodalton protein in murine macrophages.

نویسندگان

  • K L Bost
  • J D Clements
چکیده

The induction by intracellular pathogens of interleukin-12 (IL-12) secretion is of particular importance since this cytokine has been shown to be necessary for optimal cell-mediated immune responses. Several recent investigations have suggested that cultured macrophages are a significant source of IL-12 following intracellular infection with pathogens such as Salmonella spp. In an effort to critically evaluate the magnitude of the IL-12 response in cultured macrophages following interaction with Salmonella dublin, enzyme-linked immunosorbent assays specific for the 40- and 70-kDa subunits of IL-12 (IL-12p40 and IL-12p70) and a sensitive bioassay for IL-12p70 were used. Using BALB/c macrophages, S. dublin at various challenge doses was a potent inducer of IL-12p40 secretion (>6,000 pg/10(7) macrophages). However when secretion of IL-12p70 was evaluated, S. dublin did not induce comparable IL-12p70 production (<80 pg/10(7) macrophages) at any time, despite varying the challenge dose of Salmonella. The limited ability of BALB/c (Ity(s)) macrophages to secrete IL-12p70 in response to Salmonella was not a strain-specific phenomenon since similar results were demonstrated for macrophages isolated from CBA/J (Ity(r)) and C3H/HeJ (lipopolysaccharide [LPS]-hyporesponsive) mice. While intracellular infection with Salmonella was not a potent stimulus for IL-12p70 secretion in these mouse strains, macrophages from these mice responded significantly to a stimulus of gamma interferon plus LPS. Taken together these results demonstrate a limited capacity for intracellular Salmonella to stimulate murine macrophage secretion of IL-12p70, despite being a significant stimulus for IL-12p40 secretion. Furthermore, our results suggest that Salmonella-induced IL-12p40 secretion by macrophages is not solely an LPS-mediated event.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Herpes simplex virus type 2 induces secretion of IL-12 by macrophages through a mechanism involving NF-kappaB.

Interleukin (IL)-12 is an important proinflammatory and immunoregulatory cytokine expressed primarily by macrophages. Although IL-12 appears to be essential for clearance of many bacterial and parasitic infections, only little is known about the production and regulation of this cytokine during viral infections. In this study we have shown that infection of mouse macrophages with herpes simplex...

متن کامل

Role of PKC isoforms in the Fc(gamma)R-mediated inhibition of LPS-stimulated IL-12 secretion by macrophages.

Ligation of Fc receptors for immunoglobulin G (FcgammaRs) inhibits lipopolysaccharide (LPS)-stimulated secretion of interleukin (IL)-12 by macrophages. FcgammaR activation of protein kinase C (PKC) contributes to several functions of this receptor including phagocytosis, activation of the reduced nicotinamide adenine dinucleotide phosphate oxidase, and secretion of certain cytokines. Therefore,...

متن کامل

Human immunodeficiency virus gp120 inhibits interleukin-12 secretion by human monocytes: an indirect interleukin-10-mediated effect.

Interleukin-12 (IL-12), a cytokine with in vitro and in vivo immunomodulatory effects, is produced mostly by activated monocytes and macrophages. To study the effect of human immunodeficiency virus (HIV) infection on IL-12 production, we investigated the expression of IL-12 at mRNA and protein levels by human monocytes preincubated with HIV-gp120. In these conditions, we show that monocytes hav...

متن کامل

Salmonella infection does not increase expression and activity of the high affinity IL-12 receptor.

Expression of high affinity IL-12 receptors is required for IL-12-mediated IFN-gamma production. Activation of this pathway has been shown to be critical in generating optimal cell-mediated immunity. Therefore, increased IL-12 receptor expression might be expected in the host response after infection by an intracellular bacterial pathogen. In the present study, we have made the surprising disco...

متن کامل

Intestinal epithelial cells modulate antigen-presenting cell responses to bacterial DNA.

Intestinal epithelial cells and antigen-presenting cells orchestrate mucosal innate immunity. This study investigated the role of bacterial DNA in modulating epithelial and bone marrow-derived antigen-presenting cells (BM-APCs) and subsequent T-lymphocyte responses. Murine MODE-K epithelial cells and BM-APCs were treated with DNA from either Bifidobacterium breve or Salmonella enterica serovar ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Infection and immunity

دوره 65 8  شماره 

صفحات  -

تاریخ انتشار 1997