Constitutive Activation of Toll-Mediated Antifungal Defense in Serpin-Deficient Drosophila

Abstract

10. In the deiayed-saccade task, the monkey was first required to fixate a central fixation spot within a <lo error window, Immediately after fixation, a visual stimulus was presented within the RF of the neuron under study and it remained there until the end of the trial. The monkey was required t o maintain fixation on the fixation point for a delay of 1 s, while it waited for the appearance of a saccade target (0.25") at one of two locations distant from the RF. In two-thirds of the trials, the saccade target appeared when the fixation spot was extinguished and the monkey was required t o make a saccadic eye movement to the target. In the remaining trials, the saccade target did not appear; when the fixation spot was extinguished, the monkey was required to make a saccadic eye movement t o the RF stimulus. Both conditions were identical until the cue t o saccade (disappearance of the fixation spot) and were pseudorandomly interleaved. RF st'imuli were light and dark bars presented at one of four orientations (0°, 45", 90°, or 135") on a 34 X 27 cm video monitor driven by a number nine graphics board (640 X 480 resolution). Eye position was monitored at 200 Hz with a scleral search coil (77). Neural activity and eye position data were both stored for off-line analysis. The activity of single neurons was recorded by standard electrophysiological techniques described in K. Zipser, V. A. F. Lamme, and P. H. Schiller [J. Neurosci. 16, 7376 (1996)l.

Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein

“…Oregon R and y w drs-GFP dpt-LacZ 6¯i es were used as controls. Spz rm7 , Dif 2 , key 4 , dredd D55 , nec 1 , nec 2 and Toll 10b alleles are described elsewhere 6±8, 13 . Df(1)HA85/FM7c, Df(1)N105/FM6 and DaGal4 stocks were obtained from the Bloomington stock centre.…”

“…Genetic screens have identi®ed a range of genes involved in these intracellular signalling cascades 6±12 , but how they are activated by microbial infection is largely unknown. Activation of the transmembrane receptor Toll requires a proteolytically cleaved form of an extracellular cytokine-like polypeptide, Spa Ètzle 13 , suggesting that Toll does not itself function as a bona ®de recognition receptor of microbial patterns. This is in apparent contrast with the mammalian Toll-like receptors 14 and raises the question of which host molecules actually recognize microbial patterns to activate Toll through Spa Ètzle.…”

“…We used the same strategy to analyse the relationship between seml and the serine protease inhibitor nec. A loss-of-function mutation in the nec gene results in challenge-independent expression of drosomycin and in the formation of melanotic spots on the cuticle 13 . Both phenotypes are mediated by spz and Toll.…”

How Drosophila combats microbial infection: a model to study innate immunity and host–pathogen interactions

“…Even though it is now clear that the Toll and Imd pathways are selectively activated in response to different microbes, the recognition proteins that target these pathways are still unknown [27]. In contrast to some of the mammalian TLRs, Drosophila Toll does not appear to function as a direct sensor of microbial compounds, but is activated via an unknown proteolytic cascade by a small cytokine-like molecule termed Spätzle [25,51]. The receptors that activate the Imd pathway in response to Gram-negative bacteria have not been identified.…”

Nitric oxide contributes to induction of innate immune responses to gram-negative bacteria inDrosophila

“…The Drosophila Tl pathway is particularly responsive to fungi and gram-positive bacteria, which trigger processing and activation of the Tl ligand, Spaetzle (Spz; Levashina et al 1999). Tl receptor-dependent signaling activates two NF-B-related transcription factors, Dorsal (Dl) and Dorsal-related immunity factor (Dif), and expression of defense genes such as those encoding antimicrobial peptides (Lemaitre et al 1995b;Meng et al 1999).…”