TY - JOUR
T1 - Expression of IL-18 by Mycobacterium avium-infected human monocytes; association with M. avium virulence
AU - Shiratsuchi, H.
AU - Ellner, J. J.
PY - 2001
Y1 - 2001
N2 - Disseminated Mycobacterium avium infection is the most frequent bacterial infection in patients with advanced AIDS and also associated with interferon-gamma (IFN-γ) or IL-12 receptor deficiency. IFN-γ is a key cytokine in host defence against M. avium infection. Expression of IL-18, a potent IFN-γ inducer, and IFN-γ 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-γ in culture supernatants than did the SmT strain. IFN-γ 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 ± 864pg/ml, cultures with IL-18 10 ng/ml) augmented M. avium-induced IFN-γ 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 1L-18 expression by monocytes infected with the avirulent strain may result in more IFN-γ 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.
AB - Disseminated Mycobacterium avium infection is the most frequent bacterial infection in patients with advanced AIDS and also associated with interferon-gamma (IFN-γ) or IL-12 receptor deficiency. IFN-γ is a key cytokine in host defence against M. avium infection. Expression of IL-18, a potent IFN-γ inducer, and IFN-γ 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-γ in culture supernatants than did the SmT strain. IFN-γ 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 ± 864pg/ml, cultures with IL-18 10 ng/ml) augmented M. avium-induced IFN-γ 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 1L-18 expression by monocytes infected with the avirulent strain may result in more IFN-γ 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.
KW - IL-12
KW - IL-18
KW - Interferon-gamma
KW - Monocytes
KW - Mycobacterium avium
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U2 - 10.1046/j.1365-2249.2001.01411.x
DO - 10.1046/j.1365-2249.2001.01411.x
M3 - Article
C2 - 11207649
AN - SCOPUS:0035114884
SN - 0009-9104
VL - 123
SP - 203
EP - 209
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
IS - 2
ER -