Open AccessInduction of anti‐mycobacterial and anti‐listerial activity of human monocytes requires different activation signals
Author(s) -
ZERLAUTH G.,
EIBL M. M.,
MANNHALTER J. W.
Publication year - 1991
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1991.tb05688.x
Subject(s) - monocyte , listeria monocytogenes , cytokine , tumor necrosis factor alpha , immunology , recombinant dna , macrophage , incubation , biological activity , microbiology and biotechnology , antibody , biology , in vitro , medicine , biochemistry , bacteria , gene , genetics
SUMMARY The requirements Tor activation of anti‐mycobacterial and anti‐listerial activity of human monocytes were investigated, Human monocytes could be activated to display enhanced anti‐mycobacterial activity by a 24‐h treatment with Hpopolysaccharide, The mediator induced by this treatment was identified as being tumour necrosis factor‐alpha (TNF‐αAQl), Addition of recombinant TNF‐α (rTNF‐α) to the cultures of human monocytes for 24 h yielded comparable results (minimal dose required for induction of anti‐mycobacterial activity, 10 U/ml) Addition of anti‐TNF‐α antibody completely abrogated the effect, A similar treatment protocol failed to activate enhanced anti‐listerial activity, To trigger anti‐listerial activity, sequential treatment of human monocytcs with rTNF‐α and IL‐2 was required, Treatment of monocytes with 10 U/ml rTNF‐α for 24 h followed by incubation in the presence of 200 U/ml of IL‐2 for an additional 24 h yielded a reduction of listcrial growth which was moderate but statistically significant ( P < 0.00l), The activation of monocylcs observed with rTNF‐a/IL‐2 treatment was (i) dependent on both cytokincs; (ii) sequence dependent (i,e, when IL‐2 was added prior to rTNF‐α, no effect was observed); and (iii) absent in cells treated with one cytokine only, Enhancement of anti‐listerial activity by sequential use of cytokincs was not accompanied by an increase in oxidativc burst, which indicated that oxidative mechanisms were not the reason for the observed Listeria monocytogenes growth restriction, Further support for this hypothesis was obtained after intcrfcron‐gamma treatment of human monocytcs which led to an augmented PMA‐inducible release of active oxygen radicals, but was not paralleled by growth restriction of L, monocytogenes , Our results indicate that TNI‐α plays a crucial role in the activation of monocylcs for growth restriction of intraccllular microbes, Activation of human monocytcs to restrict the growth of the facultative intracellular bacteria Mycohacterium avium intracellulare and L, monocytogenes , however, follows different patterns, the initial trigger in both cases being provided by TNF‐α‐indueed signals