The earlier notion that MALP-2 or any other bacterial toll-like receptor agonists just lead to activation of NF-kappa B as the one and only transcription factor which initiates gene transcription is certainly oversimplified. On the other hand, reports appear almost daily dealing with much more complicated signal transduction pathways of toll-like receptor agonists. It has now become clear that not all toll-like receptor agonists signal in identical ways, nor are all toll-like receptors exposed on the cell surface. The pathway indicated below is but a model of how MALP-2 could be signalling.

It is based on data from my own lab as well as on those from many colleagues around the world. The advantage of such cartoons is that they simplify very complex events and that they help to connect and put into perspective seemingly independent observations. One problem with such models is that they necessarily rely on sometimes conflicting reports. Other problems arise from interpreting ones own results and those of others.

Questions arise such as, is the agonist really pure or are we possibly looking at effects of biologically active contaminants? Or else, are we looking at a primary effect of the agonist in question or do we see secondary, autocrine or paracrine effects arising from early released cytokines acting back on the system under observation? The model below ought thus to be regarded with the necessary scepticism. It is almost certain that it needs modifications and occasional updates.

Note: the reason why some target genes appear downstream of different sub-pathways results from the fact that genes require several different transcription factors in order to become activated. Note that some transcription factors are listed as such, but additionally as target (e. g. immediate early) genes.