Expression of IL-18 by Mycobacterium avium-infected human monocytes; association with M. avium virulence.
Disseminated Mycobacterium avium infection is the most frequent bacterial infection in patients with advanced AIDS and also associated with interferon-gamma (IFN-gamma) or IL-12 receptor deficiency. IFN-gamma is a key cytokine in host defence against M. avium infection. Expression of IL-18, a potent IFN-gamma inducer, and IFN-gamma by human monocytes after infection with M. avium was examined. Monocytes were co-cultured with isogenic smooth-transparent (SmT: virulent) or smooth-domed (SmD: avirulent) M. avium strains (10 organisms per monocyte). Infection with the SmD strain induced significantly higher concentration of IL-18 and IFN-gamma in culture supernatants than did the SmT strain. IFN-gamma production in response to M. avium was partially inhibited by anti-human IL-18 MoAb. Both recombinant human IL-12 (77 +/- 42 pg/ml, control versus 1492 +/- 141 pg/ml, cultures with IL-12 1 ng/ml) and IL-18 (126 +/- 37 pg/ml, control versus 2683 +/- 864 pg/ml, cultures with IL-18 10 ng/ml) augmented M. avium-induced IFN-gamma production. Freshly isolated uninfected monocytes expressed constitutive levels of IL-18. Following infection with M. avium, enhancement of IL-18 mRNA expression peaked at 3-6 h. IL-18 protein was detected in monocyte lysates as early as 1 h after infection with both SmT and SmD M. avium strains by Western blotting. Higher IL-18 expression by monocytes infected with the avirulent strain may result in more IFN-gamma production, thus modulating its pathogenicity. Local induction of IL-18 may be important both for M. avium pathogenicity and host defence and become a potential candidate for immunotherapy.
Shiratsuchi
H
H
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4984, USA. hxs4@po.cwru.edu
Ellner
J J
JJ
D002478:Cells, Cultured; D006801:Humans; D020382:Interleukin-18 / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology*; D009162:Mycobacterium avium / Q000276:immunology* / Q000472:pathogenicity; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology; D014774:Virulence / Q000276:immunology
D020382:Interleukin-18