Insect immune response to bacterial infection is mediated by eicosanoids.

Abstract

Inhibition of eicosanoid formation in larvae of the tobacco hornworm Manduca sexta, using specific inhibitors of phospholipase A2, cyclooxygenase, and lipoxygenase, severely weakened the ability of larvae to clear the bacterium Serratia marcescens from their hemolymph. The reduced capability to remove bacteria is associated with increased mortality due to these bacteria. There is a dose-dependent relationship between the phospholipase A2 inhibitor dexamethasone and both the reduced bacterial clearance and increased larval mortality. The dexamethasone effects on larval survival were reversed by treatment with arachidonic acid. Maleic acid, a nonspecific antioxidant, did not interfere with the insects' ability to remove bacterial cells from hemolymph. The larvae were shown to contain all of the C20 polyunsaturated fatty acids necessary for eicosanoid biosynthesis and to be capable of converting radioactive arachidonic acid into several primary prostaglandins. These results strongly suggest that eicosanoids mediate transduction of bacterial infection signals into the complex of cellular and humoral responses that comprise invertebrate immunity.Invertebrate immunity is an amalgam of several distinct systems, both cellular and humoral, that operate in a more or less coordinated way to provide protection from invading pathogens (1). Cellular responses include phagocytosis, encapsulation, and various cytotoxic reactions such as release of lysozyme (1, 2) and the prophenoloxidase activating system (3). These hemocyte-mediated responses are complemented by antibacterial activity, such as lectins, which occur constitutively in invertebrate hemolymph (4). In addition to normally occurring factors, several antibacterial peptides are induced by bacterial infections [namely, the cecropins (4 kDa), attacins (21 to 23 kDa), diptericins (8 kDa), and insect defensins (4 kDa)] (3,5).An important area of invertebrate immunity that has not been critically addressed concerns how the early responses to infection are mediated-that is, what is the sequence of biochemical events operative between microbial invasion and the appearance of defense mechanisms? To date, only two early steps in the immune response have been investigated. In one, immune-specific RNA was shown to be synthesized 2-4 hr after bacterial infection of the moths Hyalophora cecropia and Galleria mellonella (3). In the other, inducible lectins were synthesized in the flesh fly Sarcophaga peregrina almost immediately after their immune system was challenged (6). However, these genespecific events follow from earlier steps in transduction of bacterial invasion signals into physiological defense responses.Since many aspects of immunological defense in mammals are mediated by eicosanoid metabolites of arachidonic acid (7), we hypothesized that biosynthesis of eicosanoids is also an essential early step in mediation of the immune response in invertebrates. We tested this hypothesis by using an insect, the tobacco hornworm Manduca sexta. We report here that selective ...

Eicosanoids mediate Manduca sexta cellular response to the fungal pathogen Beauveria bassiana: A role for the lipoxygenase pathway

“…Workers in several laboratories have reversed the effects of dexamethasone on insect cellular immunity by administration of arachidonic acid (Stanley-Samuelson et al, 1991;Mandato et al 1997;Park and Kim, 2000;Dean et al, 2002). The inhibition by dexamethasone was not as pronounced as has been observed for its inhibition of bacteria-induced nodulation (Stanley-Samuelson et al, 1991;Howard et al, 1998;Miller and Stanley, 2001) nor for infection of the fungus M. anisopliae (Dean et al, 2002). Moreover, injection of arachindonic acid did not rescue the dexamethasone influence as strongly as has been observed with other challenges, including bacteria (Miller et al, 1994) and fungi (Dean et al, 2002).…”

Eicosanoids act in nodulation reactions to bacterial infections in newly emerged adult honey bees, Apis mellifera, but not in older foragers

“…We inferred from these observations that some or all of the cellular defense reactions responsible for clearing bacterial infections from hemolymph are mediated by eicosanoids (Stanley-Samuelson et al, 1991). This was the first suggestion of a signal transduction system in invertebrate cellular immunity.…”

“…While humoral and hemocytic immune reactions to bacterial infections are well documented, until recently, when there was virtually no information on the biochemical events responsible for mediating insect immune reactions. Drawing on the background of signal transduction systems in mammalian immunity, Stanley-Samuelson et al (1991) suggested insect cellular immune reactions are mediated by eicosanoids. Eicosanoids are oxygenated metabolites of arachidonic acid and two other polyunsaturated fatty acids ( Figure 1), the structures and biosynthesis of which are outlined elsewhere (Stanley, 2000).…”

Juvenile immune system activation induces a costly upregulation of adult immunity in field cricketsGryllus campestris

“…By contrast, the precursor proPO can be safely stored in high quantities and rapidly activated upon infection (Sö derhäll & Cerenius 1998). The strong upregulation of lysozyme in the haemolymph after a juvenile immune challenge may have a function as a safeguard against future reinfection or to control latent infections (Stanley-Samuelson et al 1991;Yu & Kanost 2003). Antimicrobial peptides are relatively slowly synthesized and activate a non-oxidative antimicrobial pathway without cytotoxic effects on non-target cells (Hoffmann 1995).…”