Research Article| Volume 47, ISSUE 3, P217-224, October 2003

Download started.


Campylobacter-stimulated INT407 cells produce dissociated cytokine profiles


      Objectives. To study the action of factors produced by living Campylobacter jejuni (C. jejuni) against those present within sonicated and filtrated bacteria on induction of potential cytokines by the human intestinal cell line INT407.
      Methods. We used immunohistochemical technique modified to detect intracellular production of cytokines protein and RT-PCR to read RNA messages for evaluation of de novo cytokine synthesis.
      Results. The data herein display dissociation of cytokine profiles induced on by living C. jejuni. Exposure of INT407 cells to 106 live bacteria showed the highest numbers of cytokine producing cells of all examined cytokines. IFN-γ was the highest induced cytokine followed by IL-10, TNF-α and lastly IL-4. Also, abrogation of induction of the proinflammatory cytokines IFN-γ and TNF-α but not the antiinflammatory cytokines IL-4 and IL-10 by sonicated and filtrated bacteria was depicted. At the mRNA level, TNF-α signals were noted in accordance with its protein levels since increased TNF-α mRNA signals were registered only after stimulation with living bacteria. Very low or no induction of TNF-α was registered with non-stimulated cells.
      Conclusions. These results illustrate for the first time a role for factors from living bacteria in directing the immune response towards Th1 type. Characterization of such factors may be essential for future immunotherapeutic interventions during severe bacterial infections.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Infection
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Butzler J.P.
        • Skirrow M.B.
        Campylobacter enteritis.
        Clin Gastroenterol. 1979; 8: 737-765
        • Tauxe R.V.
        Epidemiology of Campylobacter jejuni infections in the United States and other industrialized nations.
        in: Nachamkin I. Blaser M.J. Tompkins L.S. Campylobacter jejuni: current status and future trends. American Society for Microbiology, Washington, DC1992: 9-19
        • Taylor D.N.
        Campylobacter infections in developing countries.
        in: Nachamkin I. Blaser M.J. Tompkins L.S. Campylobacter jejuni: current status and future trends. American Society for Microbiology, Washington, DC1992: 20-30
        • Bacon D.J.
        • Alm R.A.
        • Burr D.H.
        • Hu L.
        • Kopecko D.J.
        • Ewing C.P.
        • Trust T.J.
        • Guerry P.
        Involvement of a plasmid in virulence of Campylobacter jejuni 81–176.
        Infect Immun. 2000; 68: 4384-4390
        • Pickett C.L.
        Campylobacter toxins and their role in pathogenesis.
        in: Nachamkin I. Blaser M.J. Campylobacter. American Society for Microbiology, Washington, DC2000: 179-190
        • Wassenaar T.M.
        Toxin production by Campylobacter.
        Clin Microbiol Rev. 1997; 10: 466-476
        • Pickett C.L.
        • Pesci E.C.
        • Cottle D.L.
        • Russell G.
        • Erdem A.N.
        • Zeytin H.
        Prevalence of cytolethal distending toxin production in Campylobacter jejuni and relatedness of Campylobacter spp. cdtB genes.
        Infect Immun. 1996; 64: 2070-2078
        • Whitehouse C.A.
        • Balbo P.B.
        • Pesci E.C.
        • Cottle D.L.
        • Mirabito P.M.
        • Pickett C.L.
        Campylobacter jejuni cytolethal distending toxin causes a G2-phase cell cycle block.
        Infect Immun. 1998; 66: 1934-1940
        • Black R.E.
        • Levine M.M.
        • Clements M.I.
        • Hughes T.P.
        • Blaser M.J.
        Experimental Campylobacter jejuni infections in humans.
        J Infect Dis. 1988; 157: 472-479
        • Pancorbo P.L.
        • de Pablo M.A.
        • Ortega E.
        • Puertollano M.A.
        • Gallego A.M.
        • Alvarez de Cienfuegos G.
        Potential intervention of Campylobacter jejuni in the modulation of murine immune response.
        Curr Microbiol. 2001; 43: 209-214
        • Abram M.
        • Vukovic D.
        • Wraber B.
        • Doric M.
        Plasma cytokine response in mice with bacterial infection.
        Mediators Inflamm. 2000; 5: 229-234
        • Bakhiet M.
        • Diab A.
        • Mustafa M.
        • Zhu J.
        • Lindqvist L.
        • Link H.
        Potential role of autoantibodies in the regulation of cytokine responses in bacterial infections.
        Infect Immun. 1997; 65: 3300-3303
        • Elkarim R.
        • Mustafa M.
        • Link H.
        • Bakhiet M.
        Recovery from Guillain–Barrié syndrome is associated with increased levels of neutralizing autoantibodies to IFN-γ.
        Clin Immunol Immunopathol. 1998; 88: 241-248
        • Sander B.
        • Andersson J.
        • Andersson U.
        Assessment of cytokines by immunofluorescence and the paraformaldehyde–saponin procedure.
        Immunol Rev. 1991; 119: 65-93
        • Lore K.
        • Sonnerborg A.
        • Spetz A.L.
        • Andersson U.
        • Andersson J.
        Immunocytochemical detection of cytokines and chemokines in Langerhans cells and in vitro derived dendritic cells.
        J Immunol Methods. 1998; 214: 97-111
        • Schulze-Koops H.
        • Kalden J.R.
        The balance of Th1/Th2 cytokines in rheumatoid arthritis.
        Best Pract Res Clin Rheumatol. 2001; 15: 677-691
        • Ishii H.
        • Tanaka H.
        • Katoh K.
        • Nakamura H.
        • Nagashima M.
        • Yoshino S.
        Characterization of infiltrating T cells and Th1/Th2-type cytokines in the synovium of patients with osteoarthritis.
        Osteoarthritis Cartilage. 2002; 10: 277-281
        • Chikano S.
        • Sawada K.
        • Shimoyama T.
        • Kashiwamura S.I.
        • Sugihara A.
        • Sekikawa K.
        • Terada N.
        • Nakanishi K.
        • Okamura H.
        IL-18 and IL-12 induce intestinal inflammation and fatty liver in mice in an IFN-gamma dependent manner.
        Gut. 2001; 48: 6-7
        • Bao S.
        • Beagley K.W.
        • France M.P.
        • Shen J.
        • Husband A.J.
        Interferon-gamma plays a critical role in intestinal immunity against Salmonella typhimurium infection.
        Immunology. 2000; 99: 464-472
        • Raqib R.
        • Gustafsson A.
        • Andersson J.
        • Bakhiet M.
        A systemic downregulation of gamma interferon production is associated with acute shigellosis.
        Infect Immun. 1997; 65: 5338-5341
        • Raqib R.
        • Ljungdahl A.
        • Lindberg A.A.
        • Andersson U.
        • Andersson J.
        Local entrapment of interferon gamma in the recovery from Shigella dysenteriae type 1 infection.
        Gut. 1996; 38: 328-336
        • Carol L.
        Campylobacter toxins and their role in pathogenesis.
        in: Nachimakin I. Blaser M.J. Campylobacter. 2nd ed. American Society for Microbiology, Washington DC, USA2000
        • Denis M.
        • Cambell D.
        • Gregg E.G.
        Interleukin-2 and granulocyte-macrophage colony-stimulating factor stimulate growth of a virulent strain of Escherichia coli.
        Infect Immun. 1991; 59: 1853-1856
        • Porat R.
        • Clark B.D.
        • Wolff S.M.
        • Dinarello C.A.
        Enhancement of growth of virulent strains of Escherichia coli by interleukin-1.
        Science. 1991; 254: 430-432
        • Denis M.
        Interleukin-6 is used as a growth factor by virulent Mycobacterium avium: presence of specific receptors.
        Cell Immunol. 1992; 141: 182-188
        • Bakhiet M.
        • Olsson T.
        • Mhlanga J.
        • Büscher P.
        • Lycke N.
        • Van der Meide P.
        • Kristensson K.
        Human and rodent IFN-γ as a growth factor for Trypanosoma brucei brucei.
        Eur J Immunol. 1996; 26: 1359-1364
        • Amiri P.
        • Locksley R.M.
        • Parslow T.G.
        • Sadick M.
        • Rector E.
        • Ritter D.
        • McKerrow J.H.
        Tumor necrosis factor α restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice.
        Nature. 1992; 356: 604-607
        • Lee J.D.
        • Rhoades K.
        • Economou J.S.
        Interleukin-4 inhibits the expression of tumour necrosis factors alpha and beta, interleukins-1 beta and-6 and interferon-gamma.
        Immunol Cell Biol. 1995; 73: 57-61
        • Paul W.E.
        Interleukin 4/B cell stimulatory factor 1: one lymphokine, many functions.
        Faseb J. 1987; 1: 456-461
        • Fiorentino D.F.
        • Bond M.W.
        • Mosmann T.R.
        Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones.
        J Exp Med. 1989; 170: 2081-2095
        • Fiorentino D.F.
        • Zlotnik A.
        • Mosmann T.R.
        • Howard M.
        • Moore K.W.
        • O'Garra A.
        IL-10 inhibits cytokine production by activated macrophages.
        J Immunol. 1991; 146: 3444-3451
        • Schopf L.R.
        • Hoffmann K.F.
        • Cheever A.W.
        • Urban Jr., J.F.
        • Wynn T.A.
        IL-10 is critical for host resistance and survival during gastrointestinal helminth infection.
        J Immunol. 2002; 168: 2383-2392
        • Schmitz H.
        • Fromm M.
        • Bode H.
        • Scholz P.
        • Riecken E.O.
        • Schulzke J.D.
        Tumor necrosis factor-alpha induces Cl− and K+ secretion in human distal colon driven by prostaglandin E2.
        Am J Physiol. 1996; 271: 669-674
        • Mijatovic T.
        • Kruys V.
        • Caput D.
        • Defrance P.
        • Huez G.
        Interleukin-4 and -13 inhibit tumor necrosis factor-alpha mRNA translational activation in lipopolysaccharide-induced mouse macrophages.
        J Biol Chem. 1997; 272: 14394-14398