scholarly journals The Peptidoglycan Recognition Proteins PGRPLA and PGRPLB Regulate Anopheles Immunity to Bacteria and Affect Infection by Plasmodium

2017 ◽  
Vol 9 (4) ◽  
pp. 333-342 ◽  
Author(s):  
Mathilde Gendrin ◽  
Fanny Turlure ◽  
Faye H. Rodgers ◽  
Anna Cohuet ◽  
Isabelle Morlais ◽  
...  

Peptidoglycan recognition proteins (PGRPs) form a family of immune regulators that is conserved from insects to mammals. In the malaria vector mosquito Anophelescoluzzii, the peptidoglycan receptor PGRPLC activates the immune-deficiency (Imd) pathway limiting both the microbiota load and Plasmodium infection. Here, we carried out an RNA interference screen to examine the role of all 7 Anopheles PGRPs in infections with Plasmodium berghei and P. falciparum. We show that, in addition to PGRPLC, PGRPLA and PGRPS2/PGRPS3 also participate in antiparasitic defenses, and that PGRPLB promotes mosquito permissiveness to P. falciparum. We also demonstrate that following a mosquito blood feeding, which promotes growth of the gut microbiota, PGRPLA and PGRPLB positively and negatively regulate the activation of the Imd pathway, respectively. Our data demonstrate that PGRPs are important regulators of the mosquito epithelial immunity and vector competence.

2020 ◽  
Author(s):  
Mengfei Wang ◽  
Jingwen Wang

Abstract Background: Sugar feeding provides energy for mosquitoes. Facilitated glucose transporters (GLUTs) are responsible for the uptake of glucose in animals. However, the knowledge of GLUTs function in Anopheles mosquito is limited. Methods: Phylogenetic analysis of GLUTs in Anopheles stephensi (Asteglut) was performed by the maximum likelihood and Bayesian method. The spatial and temporal expression patterns of the four Astegluts were analyzed by qPCR. The function of Asteglut1 was examined using a dsRNA-mediated RNA interference method. Transcriptome analysis was used to investigate the global influence of Asteglut1 on mosquito physiology. Results: We identified 4 glut genes, Asteglut1 , Asteglutx , Asteglut3 and Asteglut4 in An. stephensi . Asteglut1, Asteglut3 and Asteglut4 were mainly expressed in the midgut. Plasmodium berghei infection differentially regulated the expression of Astegluts with significant downregulation of Asteglut1 and Asteglut4 , while upregulation of Asteglutx . Only knocking down Asteglut1 facilitated Plasmodium berghei infection in An. stephensi . This might be due to the accumulation of glucose prior to blood feeding in dsAsteglut1-treated mosquitoes. Our transcriptome analysis revealed that knockdown of Asteglut1 differentially regulated expression of genes associated with multiple functional clusters, especially those related to detoxification and immunity. The dysregulation of multiple pathways might contribute to the increased P. berghei infection. Conclusions: Our study shows that Asteglut1 participates in defense against P. berghei in An. stephensi . The regulation of Asteglut1 on vector competence might through modulating multiple biological processes, such as detoxification and immunity.


2020 ◽  
Author(s):  
Mengfei Wang ◽  
Jingwen Wang

Abstract Background: Sugar feeding provides energy for mosquitoes. Facilitated glucose transporters (GLUTs) are responsible for the uptake of glucose in animals. However, the knowledge of GLUTs function in Anopheles mosquito is limited. Methods: Phylogenetic analysis of GLUTs in Anopheles stephensi (Asteglut) was performed by the maximum likelihood and Bayesian method. The spatial and temporal expression patterns of the four Astegluts were analyzed by qPCR. The function of Asteglut1 was examined using a dsRNA-mediated RNA interference method. Transcriptome analysis was used to investigate the global influence of Asteglut1 on mosquito physiology. Results: We identified 4 glut genes, Asteglut1 , Asteglutx , Asteglut3 and Asteglut4 in An. stephensi . Asteglut1, Asteglut3 and Asteglut4 were mainly expressed in the midgut. Plasmodium berghei infection differentially regulated the expression of Astegluts with significant downregulation of Asteglut1 and Asteglut4 , while upregulation of Asteglutx . Only knocking down Asteglut1 significantly increased the susceptibility of An. stephensi to Plasmodium berghei infection. This might be due to the accumulation of glucose prior to blood feeding in dsAsteglut1-treated mosquitoes. Our transcriptome analysis revealed that knockdown of Asteglut1 differentially regulated expression of genes associated with multiple functional clusters including detoxification and immunity. The dysregulation of multiple pathways might contribute to the increased P. berghei infection. Conclusions: Our study shows that Asteglut1 is essential in defense against P. berghei in An. stephensi . The regulation of Asteglut1 on vector competence might through modulating multiple biological processes, including detoxification and immunity.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rebekah A. Reynolds ◽  
Hyeogsun Kwon ◽  
Thiago Luiz Alves e Silva ◽  
Janet Olivas ◽  
Joel Vega-Rodriguez ◽  
...  

AbstractMosquito physiology and immunity are integral determinants of malaria vector competence. This includes the principal role of hormonal signaling in Anopheles gambiae initiated shortly after blood-feeding, which stimulates immune induction and promotes vitellogenesis through the function of 20-hydroxyecdysone (20E). Previous studies demonstrated that manipulating 20E signaling through the direct injection of 20E or the application of a 20E agonist can significantly impact Plasmodium infection outcomes, reducing oocyst numbers and the potential for malaria transmission. In support of these findings, we demonstrate that a 20E agonist, halofenozide, is able to induce anti-Plasmodium immune responses that limit Plasmodium ookinetes. We demonstrate that halofenozide requires the function of ultraspiracle (USP), a component of the canonical heterodimeric ecdysone receptor, to induce malaria parasite killing responses. Additional experiments suggest that the effects of halofenozide treatment are temporal, such that its application only limits malaria parasites when applied prior to infection. Unlike 20E, halofenozide does not influence cellular immune function or AMP production. Together, our results further demonstrate the potential of targeting 20E signaling pathways to reduce malaria parasite infection in the mosquito vector and provide new insight into the mechanisms of halofenozide-mediated immune activation that differ from 20E.


mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Isabelle Louradour ◽  
Kashinath Ghosh ◽  
Ehud Inbar ◽  
David L. Sacks

ABSTRACT Sand flies are the natural vectors for the Leishmania species that produce a spectrum of diseases in their mammalian hosts, including humans. Studies of sand fly/Leishmania interactions have been limited by the absence of genome editing techniques applicable to these insects. In this report, we adapted CRISPR (clustered regularly interspaced palindromic repeat)/Cas9 (CRISPR-associated protein 9) technology to the Phlebotomus papatasi sand fly, a natural vector for Leishmania major, targeting the sand fly immune deficiency (IMD) pathway in order to decipher its contribution to vector competence. We established a protocol for transformation in P. papatasi and were able to generate transmissible null mutant alleles for Relish (Rel), the only transcription factor of the IMD pathway. While the maintenance of a homozygous mutant stock was severely compromised, we were able to establish in an early generation their greater susceptibility to infection with L. major. Flies carrying different heterozygous mutant alleles variably displayed a more permissive phenotype, presenting higher loads of parasites or greater numbers of infective-stage promastigotes. Together, our data show (i) the successful adaptation of the CRISPR/Cas9 technology to sand flies and (ii) the impact of the sand fly immune response on vector competence for Leishmania parasites. IMPORTANCE Sand flies are the natural vectors of Leishmania parasites. Studies of sand fly/Leishmania interactions have been limited by the lack of successful genomic manipulation of these insects. This paper shows the first example of successful targeted mutagenesis in sand flies via adaptation of the CRISPR/Cas9 editing technique. We generated transmissible null mutant alleles of relish, a gene known to be essential for the control of immune response in other insects. In addition to the expected higher level of susceptibility to bacteria, the mutant flies presented higher loads of parasites when infected with L. major, showing that the sand fly immune response impacts its vector competence for this pathogen.


Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1013 ◽  
Author(s):  
Ciota ◽  
Keyel

We reviewed the literature on the role of temperature in transmission of zoonotic arboviruses. Vector competence is affected by both direct and indirect effects of temperature, and generally increases with increasing temperature, but results may vary by vector species, population, and viral strain. Temperature additionally has a significant influence on life history traits of vectors at both immature and adult life stages, and for important behaviors such as blood-feeding and mating. Similar to vector competence, temperature effects on life history traits can vary by species and population. Vector, host, and viral distributions are all affected by temperature, and are generally expected to change with increased temperatures predicted under climate change. Arboviruses are generally expected to shift poleward and to higher elevations under climate change, yet significant variability on fine geographic scales is likely. Temperature effects are generally unimodal, with increases in abundance up to an optimum, and then decreases at high temperatures. Improved vector distribution information could facilitate future distribution modeling. A wide variety of approaches have been used to model viral distributions, although most research has focused on the West Nile virus. Direct temperature effects are frequently observed, as are indirect effects, such as through droughts, where temperature interacts with rainfall. Thermal biology approaches hold much promise for syntheses across viruses, vectors, and hosts, yet future studies must consider the specificity of interactions and the dynamic nature of evolving biological systems.


2020 ◽  
Author(s):  
Rebekah A. Reynolds ◽  
Hyeogsun Kwon ◽  
Thiago Luiz Alves e Silva ◽  
Janet Olivas ◽  
Joel Vega-Rodriguez ◽  
...  

AbstractMosquito physiology and immunity are integral determinants of malaria vector competence. This includes the principal role of hormonal signaling in Anopheles gambiae initiated shortly after blood-feeding, which stimulates immune induction and promotes vitellogenesis through the function of 20-hydroxyecdysone (20E). Previous studies demonstrated that manipulating 20E signaling through the direct injection of 20E or the application of a 20E agonist can significantly impact Plasmodium infection outcomes, reducing oocyst numbers and the potential for malaria transmission. In support of these findings, we demonstrate that a 20E agonist, halofenozide, is able to induce anti-Plasmodium immune responses that limit Plasmodium ookinetes. We demonstrate that halofenozide requires the function of ultraspiracle (USP), a component of the canonical heterodimeric ecdysone receptor, to induce malaria parasite killing responses. Additional experiments suggest that the effects of halofenozide treatment are temporal, such that its application only limits malaria parasites when applied prior to infection. Unlike 20E, halofenozide does not influence cellular immune function or AMP production. Together, our results further demonstrate the potential of targeting 20E signaling pathways to reduce malaria parasite infection in the mosquito vector and provide new insight into the mechanisms of halofenozide-mediated immune activation that differ from 20E.


2020 ◽  
Author(s):  
Mengfei Wang ◽  
Jingwen Wang

Abstract Background: Sugar-feeding provides energy for mosquitoes. Facilitated glucose transporters (GLUTs) are responsible for the uptake of glucose in animals. However, knowledge of GLUTs function in Anopheles spp. is limited. Methods: Phylogenetic analysis of GLUTs in Anopheles stephensi was performed by the maximum likelihood and Bayesian inference methods. The spatial and temporal expression patterns of four Asteglut genes were analyzed by qPCR. The function of Asteglut1 was examined using a dsRNA-mediated RNA interference method. Transcriptome analysis was used to investigate the global influence of Asteglut1 on mosquito physiology.Results: We identified 4 glut genes, Asteglut1, Asteglutx, Asteglut3 and Asteglut4 in An. stephensi. Asteglut1, Asteglut3 and Asteglut4 were mainly expressed in the midgut. Plasmodium berghei infection differentially regulated the expression of Asteglut genes with significant downregulation of Asteglut1 and Asteglut4, while upregulation of Asteglutx. Only knocking-down Asteglut1 facilitated Plasmodium berghei infection in An. stephensi. This might be due to the accumulation of glucose prior to blood-feeding in dsAsteglut1-treated mosquitoes. Our transcriptome analysis revealed that knockdown of Asteglut1 differentially regulated expression of genes associated with multiple functional clusters, especially those related to detoxification and immunity. The dysregulation of multiple pathways might contribute to the increased P. berghei infection. Conclusions: Our study shows that Asteglut1 participates in defense against P. berghei in An. stephensi. The regulation of Asteglut1 on vector competence might through modulating multiple biological processes, such as detoxification and immunity.


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