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: 5.03). 07/2006; 60(5):1194-204. DOI: 10.1111/j.1365-2958.2006.05180.x
Source: PubMed

ABSTRACT 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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    • "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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    • "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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    • "Production of recombinant TAg5 in Sf9 insect cells allowed us to explore the correlation between human IgE responses and exposure to tsetse fly bites. In addition, we have optimized an RNA interference approach for the specific silencing of tsetse fly salivary proteins, similar to a procedure described for the knock-down of an antimicrobial peptide in the fat body tissue (Hu and Aksoy, 2006). Using a single thoracic injection of 15 mg Fig. 6. "
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    ABSTRACT: Our previous screening of a Glossina morsitans morsitans lamdagt11 salivary gland expression library with serum of a tsetse fly exposed rabbit identified a cDNA encoding Tsetse Antigen5 (TAg5, 28.9 kDa), a homologue of Antigen5 sting venom allergens. Recombinant TAg5 was produced in Sf9 cells in order to assess its immunogenic properties in humans. Plasma from a patient that previously exhibited anaphylactic reactions against tsetse fly bites contained circulating anti-TAg5 and anti-saliva IgEs. In a significant proportion of plasma samples of African individuals, TAg5 and saliva binding IgEs (respectively 56 and 65%) can be detected. Saliva, harvested from flies that were subjected to TAg5- specific RNA interference (RNAi), displayed significantly reduced IgE binding potential. Allergenic properties of TAg5 and tsetse fly saliva were further illustrated in immunized mice, using an immediate cutaneous hypersensitivity and passive cutaneous anaphylaxis assay. Collectively, TAg5 was illustrated to be a tsetse fly salivary allergen, demonstrating that Antigen5-related proteins are represented as functional allergens not only in stinging but also in blood feeding insects.
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