Hu C, Aksoy S.. Innate immune responses regulate trypanosome parasite infection of the tsetse fly Glossina morsitans morsitans. Mol Microbiol 60: 1194-1204

Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College St., 606 LEPH, New Haven, CT 06510, USA.
Molecular Microbiology (Impact Factor: 4.42). 07/2006; 60(5):1194-204. DOI: 10.1111/j.1365-2958.2006.05180.x
Source: PubMed


Tsetse flies transmit the protozoan parasite African trypanosomes, the agents of human sleeping sickness in sub-Saharan Africa. Parasite transmission in the insect is restricted by a natural resistance phenomenon (refractoriness). Understanding the mechanism of parasite resistance is important as strengthening fly's response(s) via transgenic approaches can prevent parasite transmission and lead to the development of novel vector control strategies. Here, we investigated the role of one of the two major pathways regulating innate immunity in invertebrates, the immunodeficiency (Imd) pathway, for Glossina morsitans morsitans's natural defence against Trypanosoma brucei spp. infections. We determined the molecular structure of the Imd pathway transcriptional activator Relish (GmmRel), which shows high amino acid identity and structural similarity to its Drosophila homologue. Through a double-stranded RNA-based interference approach, we showed that the pathogen-induced expression profile of the antimicrobial peptides (AMPs) attacin and cecropin is under the regulation of GmmRel. Unexpectedly, the AMP diptericin appears to be constitutively expressed in tsetse independent of the presence of the Rel factor. Through GmmRel knock-down, we could successfully block the induction of attacin and cecropin expression in the immune responsive tissues fat body and proventriculus (cardia) following microbial challenge. The midgut and salivary gland trypanosome infection prevalence, as well as the intensity of midgut parasite infections were found to be significantly higher in flies when attacin and relish expression were knocked down. Our results provide the first direct evidence for the involvement of antimicrobial peptides in trypanosome transmission in tsetse.

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Available from: Changyun Hu, Feb 26, 2014
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    • "To confirm the role in tsetse refractoriness, attacin knockdown by RNAi increased both midgut and salivary gland infections. This was the first time an HDP was directly linked to parasite transmission (Hu and Aksoy, 2006). The observed delay in HDP activation by ingested trypanosomes may be exacerbated in teneral flies as a result of an immature immune system and minimal lipid resources present in the fat body. "
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    ABSTRACT: Tsetse flies are the most important vectors of African trypanosomiasis but, surprisingly, are highly refractory to trypanosome parasite infection. In populations of wild caught flies, it is rare to find mature salivarian and mouthpart parasite infection rates exceeding 1 and 15%, respectively. This inherent refractoriness persists throughout the lifespan of the fly, although extreme starvation and suboptimal environmental conditions can cause a reversion to the susceptible phenotype. The teneral phenomenon is a phenotype unique to newly emerged, previously unfed tsetse, and is evidenced by a profound susceptibility to trypanosome infection. This susceptibility persists for only a few days post-emergence and decreases with fly age and bloodmeal acquisition. Researchers investigating trypanosome-tsetse interactions routinely exploit this phenomenon by using young, unfed (teneral) flies to naturally boost trypanosome establishment and maturation rates. A suite of factors may contribute, at least in part, to this unusual parasite permissive phenotype. These include the physical maturity of midgut barriers, the activation of immunoresponsive tissues and their effector molecules, and the role of the microflora within the midgut of the newly emerged fly. However, at present, the molecular mechanisms that underpin the teneral phenomenon still remain unknown. This review will provide a historical overview of the teneral phenomenon and will examine immune-related factors that influence, and may help us better understand, this unusual phenotype.
    Full-text · Article · Nov 2013 · Frontiers in Cellular and Infection Microbiology
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    • "Indeed, in all existing vector populations natural refractoriness to infection by a pathogen occurs as a result of the arthropod's innate immune system. RNA interference studies targeting the positive or negative regulators of the major immune signalling pathways (Toll, IMD and the Jak/Stat pathway) have illustrated their importance in various vector/pathogen combinations (Garver et al., 2009; Hu and Aksoy, 2006; Souza-Neto et al., 2009; Wang et al., 2009; Zou et al., 2011). Strikingly, RNAi silencing of cactus, a negative regulator of the Toll pathway, is sufficient to boost the basal immunity to sterile immunity of A. gambiae to Plasmodium berghei (Frolet et al., 2006). "
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    ABSTRACT: Blood feeding arthropods are responsible for the transmission of a large array of medically important infectious agents that include viruses, bacteria, protozoan parasites and helminths. The recent development of transgenic and paratransgenic technologies have enabled supplementing the immune system of these arthropod vectors with anti-pathogen effector molecules in view of compromising their vector competence for these microbial agents. The characteristics of the selected anti-pathogen compound will largely determine the efficacy and specificity of this approach. Low specificity will generally result in bystander effects, likely having a direct or indirect fitness cost for the arthropod. In contrast, the use of highly specific compounds from the adaptive immune system of vertebrates such as antibody derived fragments is more likely to enable highly specific effects without conferring a selective disadvantage to the (para)transgenic arthropods. Here, Nanobodies® are excellent candidates to increase the immune competence of arthropods. Moreover they were shown to exert a novel type of anti-pathogen activity that uniquely depends on their small size.
    Full-text · Article · Jul 2012 · Journal of Invertebrate Pathology
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    • "The factors involved in establishment are largely unknown and those involved in maturation are unclear. Nevertheless, among factors involved in vector competence appear to be the sex of the fly [6] [7], the trypanosome genotype [8], the tsetse intestinal lectin [9] [10], and the tsetse immune responses [11]. More recently, antioxidants have been shown to greatly increase midgut trypanosome infection rates in tsetse [12], suggesting that oxidative stress plays a role in the refractoriness of tsetse to trypanosome infection. "
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    ABSTRACT: Trypanosoma secretome was shown to be involved in parasite virulence and is suspected of interfering in parasite life-cycle steps such as establishment in the Glossina midgut, metacyclogenesis. Therefore, we attempted to identify the proteins secreted by procyclic strains of T. brucei gambiense and T. brucei brucei, responsible for human and animal trypanosomiasis, respectively. Using mass spectrometry, 427 and 483 nonredundant proteins were characterized in T. brucei brucei and T. brucei gambiense secretomes, respectively; 35% and 42% of the corresponding secretome proteins were specifically secreted by T. brucei brucei and T. brucei gambiense, respectively, while 279 proteins were common to both subspecies. The proteins were assigned to 12 functional classes. Special attention was paid to the most abundant proteases (14 families) because of their potential implication in the infection process and nutrient supply. The presence of proteins usually secreted via an exosome pathway suggests that this type of process is involved in trypanosome ESP secretion. The overall results provide leads for further research to develop novel tools for blocking trypanosome transmission.
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