They also observed an attenuation of PLA2 activities in em R

They also observed an attenuation of PLA2 activities in em R

They also observed an attenuation of PLA2 activities in em R. them. The most well known pathogen-associated molecular patterns (PAMPs) are microbial cell-wall components like lipopolysaccharides (LPS) of Gram-negative bacteria, lipoteichoic acid and peptidoglycans of Gram-positive bacteria, -1,3 glucans from fungi as well as glycosylphosphatidylinositol (GPI) from protozoan parasites [1,2]. The humoral immune system recognizes PAMPs by pattern recognition receptors which are conserved in evolution to bind unique products of microbial metabolism not produced by the host [1,2]. The humoral pattern recognition receptors such as LPS-binding proteins, peptidoglycan recognition RN486 proteins (PGRPs), Gram-negative binding proteins (GNBPs), 1,3-glucans recognition protein (GRP), circulates in the hemolymph of insects [3,4]. In the hemocyte surface there are several proteins implicated in the cellular immune response against invading microbes by recognizing the PAMPs. The most well known cellular receptors involved in recognition of pathogens in several insect species are croquemort (homologue of the mammalian CD36 family), Down syndrome cell-adhesion molecule RN486 (Dscam), peptidoglycan recognition protein (PGRP-LC), Eater (transmembrane protein) and the Toll family members [3,4]. Humoral immunity em Drosophila melanogaster /em , a dipteran, has become an appropriate model for the investigation of immune pathways and insect-microorganism interactions [4-6]. Apparently, the main components of the core signaling processes are conserved between insects [4]. The genome sequencing of these insects allowed a comparative genomic analysis of the gene families involved in the em Drosophila /em defence reactions [7]. The best-characterized insect humoral response is the production of antimicrobial peptides (AMPs). These peptides are small, cationic and with different structures. They are released into the hemolymph during contamination [8]. The main source of AMPs is from the fat body, but several epithelia RN486 and insect organs are also able to produce these substances [9]. The most important AMPs are defensins which act mainly against Gram-positive bacteria [10]. However, cecropins that have a large spectrum are more effective against Gram-negative bacteria [11]. There are other AMPs like attacin, diptericin, drosocin and drosomycin, etc [5,12]. Most AMPs have simple and non-specific modes of antibiotic action, such as driving pathogen membrane disruption by altering the membrane permeabilization or through an intracellular target [10-12]. Investigation in em Drosophila /em exhibited that production of AMPs is related to two distinct pathways: Toll and IMD pathways [3]. Recent studies suggested that these two pathways respond respectively to Gram-positive or Gram-negative bacteria and fungal infections in insects [5,12]. A third pathway involved in immune reactions, especially in mammals, is the JAK/STAT (Janus kinase/Signal transducer and activator of transcription) [13]. The JAK/STAT signaling pathway takes place mainly in the excess fat body of insects. The production of AMPs is usually a common result of JAK/STAT, Toll and Imd pathway activity [14] (Physique ?(Figure11). Open in a separate window Physique INHA 1 Toll, IMD and JAK-STAT pathways. Insect tissues recognize pathogen-associated molecular patterns (PAMPs) by transmembrane receptors (DOME, Toll and PGRPs) in plasmatic membrane (PM) that activate the three pathways. The JAK-STAT pathway is usually activated by the receptor DOME ( em domeless /em ) that transduces the signal to JAK and the cytosolic STAT. The Toll pathway starts with activation of RN486 the receptor Toll that signals to the cleavage of Dorsal-related immunity factor (DIF) complex releasing DIF. The IMD pathway through peptidoglycan recognition proteins (PGRPs) activates IMD (immune deficiency) that regulates the proteolytic cleavage and.