Trypanosoma rangeli: a new perspective for studying the modulation of immune reactions of Rhodnius prolixus

Abstract

Insects are exposed to a wide range of microorganisms (bacteria, fungi, parasites and viruses) and have interconnected powerful immune reactions. Although insects lack an acquired immune system they have well-developed innate immune defences that allow a general and rapid response to infectious agents.Over the last few decades we have observed a dramatic increase in the knowledge of insect innate immunity, which relies on both humoral and cellular responses. However, innate reactions to natural insect pathogens and insect-transmitted pathogens, such as parasites, still remain poorly understood.In this review, we briefly introduce the general immune system of insects and highlight our current knowledge of these reactions focusing on the interactions of Trypanosoma rangeli with Rhodnius prolixus, an important model for innate immunity investigation.

Figure 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 activated by the receptor DOME (domeless) that transduces the signal to JAK and the cytosolic STAT. The Toll pathway starts with activation of 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 activation of Relish. The transcription factors (STAT, DIF and Relish) translocate to the nucleus through the nuclear membrine activating the expression of its transcriptional targets resulting in the production of antimicrobial peptides and other immune responses.

Figure 2

A serine proteinase cascade is activated when different receptors recognize pathogen-associated molecular patterns (PAMPs). These serine proteases hydrolyze and activate the prophenoloxidase-activating proteinase precursor (proPAP) to prophenoloxidase-activating proteinase (PAP) that can be inhibited by serpins (proteinase inhibitors). The enzyme PAP hydrolyses prophenoloxidase (PPO) releasing phenoloxidase (PO). PO oxidizes tyrosine to dihydroxyphenylalanine (DOPA) and subsequently into quinones, the precursors of melanin, cytotoxic products and encapsulation of pathogens.

Figure 3

Phospholipids are hydrolyzed by phospholipase A₂ liberating arachidonic acid and Lyso-PAF, regulators of insect's immune system. Arachidonic acid is the substrate for eicosanoid production, prostaglandins via cyclooxygenase and leukotrienes via lipoxygenase. Lyso-PAF is acetylated by PAF-acetyl transferase releasing PAF that can be degraded by PAF-acetyl hydrolase that hydrolyses PAF regenerating Lyso-PAF. In the presence of dexamethasone the immune responses are inhibited due to the suppression of phospholipase A₂ activity with lower production of eicosanoids and PAF. On the other hand when exogenous arachidonic acid is added there is enhancement of eicosanoid production and immune responses increase.

Figure 4

Scheme of biological cycle of Trypanosoma rangeli within its insect vector. The insect feeds on blood infected with trypomastigote forms which differentiate to epimastigotes in the midgut (white arrows) where they multiply (1). Some epimastigotes invade the hemolymph through the gut epithelium (red arrow). Long and short forms of epimastigotes can entry into the hemocytes and multiply or replicate in the plasma (2). Some parasites invade the salivary glands (blue arrow) and differentiate to trypomastigotes which will be transmitted when the insect-vector feeds on another host (3).

Figure 5

A schematic illustration of Trypanosoma rangeli regulating the Rhodnius prolixus immune reactions. White arrows (↓) indicate immune reactions decrease after infection of R. prolixus with T. rangeli. In the case of AMP production by R. prolixus, there is no known (?) regulation by T. rangeli.