The IMD Pathway

The immune deficiency (IMD) pathway is reminiscent of the vertebrate tumour necrosis factor (TNF)-a pathway (Khush et al., 2001; Silverman & Maniatis, 2001) and derives its name from the first mutation with impaired response to Gram-negative bacteria (Lemaitre et al., 1995). It is thought that the peptidoglycan recognition protein (PGRP) is a co-receptor in the IMD pathway (Gottar et al., 2002). Also Drosophila homologues of the TNF-a receptor, Wengen, and its ligand, Eiger, have been isolated but there is no current knowledge of their involvement in the IMD pathway (Kauppila et al., 2003; Kanda et al., 2002; Igaki et al., 2002). The IMD pathway activates the NF-k-like transcription factor Relish (Hedengren et al., 1999). In order for Relish to translocate to the nucleus, its C-terminal inhibitory portion has to be removed (Stoven et al., 2000). In contrast to vertebrate counterparts and to cactus, Relish activation does not require the proteolytic breakdown of its inhibitor, just its dissociation. In mammals, a TNF-a stimulus induces the assembly of the receptor, a part of a large receptor-adaptor complex, which includes the receptor integrating protein (RIP), Fas-associated DD (FADD) and caspase 8. The homologues of these proteins, IMD, dFADD (Hu et al., 2000; Leulier et al., 2002; Naitza et al., 2002) and the death-related ced-3/NEDD2-like protein (DREDD) (Leulier et al., 2000) are required for Relish activation after Gram-negative infection. The favoured hypothesis of IMD activation is that the IMD-dFADD-DREDD complex is formed following PGRP activation (Leclerc & Reichhart, 2004). The activation of this adaptor complex induces the activation of Drosophila transforming growth factor-activated protein kinase 1 (dTAK1) (Vidal et al., 2001). This dTAK1 is a homologue of TAK1, a mitogen-activated protein kinase kinase kinase (MAPKKK) involved in the signal transduction pathways of vertebrates, including the c-Jun N-terminal kinase (JNK) and the NF-a pathways. The IMD pathway in insects is activated on the most part by Gram-negative bacteria and initiates the transcription of mainly antibacterial peptides such as diptericin

(Lee et al., 2001). This immune-inducing pathway is still poorly understood and there are probably multiple factors involved in the pathway still unidentified.

Cure Your Yeast Infection For Good

Cure Your Yeast Infection For Good

The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.

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