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

Gendrin, Mathilde; Turlure, Fanny; Rodgers, Faye H.; Cohuet, Anna; Morlais, Isabelle; Christophides, George K.

doi:10.1159/000452797

Cited by 48 publications

(60 citation statements)

References 26 publications

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“…We also noticed the signi cant induction of caudal, and reduction of pgrps, pgrp-la, pgrp-lc, pgrp-ld, and the antimicrobial peptides, defensin in dsAsteglut1-treated mosquitoes, suggesting that Asteglut1 might be involved in regulation of immune responses [25,40,56]. PGRP-LA is a receptor of the mosquito immune de ciency pathway (Imd) [41]. It helps to control the homeostasis of gut microbiota and parasite infection in An.…”

Section: Discussionmentioning

confidence: 93%

“…Five immune related genes were differentially regulated. Caudal, the negative regulator of Imd pathway was signi cantly upregulated (P = 0.0337) [40], while the peptidoglycan recognition proteins, pgrp-la, -lc,ld, and the antimicrobial peptides, defensin were signi cantly downregulated (P = 0.0111, P = 0.0378, P = 0.0022) [25,[40][41][42][43]. These results indicate that Asteglut1 might control parasite infection by regulating mosquito immune responses.…”

Section: Transcriptional Analysis Of Asteglut1-knockdown Mosquitoesmentioning

confidence: 89%

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Glucose transporter GLUT1 influences Plasmodium berghei infection in Anopheles stephensi

Wang

2020

Preprint

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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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Section: Discussionmentioning

confidence: 93%

Section: Transcriptional Analysis Of Asteglut1-knockdown Mosquitoesmentioning

confidence: 89%

Glucose transporter GLUT1 influences Plasmodium berghei infection in Anopheles stephensi

Wang

2020

Preprint

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“…In the ensuing cytoplasmic cascade, NF-κB transcription factor Rel2 is phosphorylated by IKK2 and cleaved by DREDD to induce its nuclear translocation. IMD pathway is repressed by Caspar (Sim et al, 2014), an Ectoderm-expressed 4-containing module (Ect4) (Akhouayri et al, 2011) and PGRP-LB (Gendrin et al, 2017). We observed an induction of IMD pathway by DENV and ZIKV through PGRP-LB downregulation, and by CHIKV through Caspar downregulation and IKK2 upregulation (Figure 1c).…”

Section: Resultsmentioning

confidence: 99%

JNK pathway restricts DENV, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands

Chowdhury

Modahl

Tan

et al. 2020

Preprint

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150 words) 23 Arbovirus infection of Aedes aegypti salivary glands (SGs) determines transmission. 24 However, there is a dearth of knowledge on SG immunity. Here, we characterized SG 25 immune response to dengue, Zika and chikungunya viruses using high-throughput 26 transcriptomics. The three viruses regulate components of Toll, IMD and JNK pathways. 27 However, silencing of Toll and IMD components showed variable effects on SG infection by 28 each virus. In contrast, regulation of JNK pathway produced consistent responses. Virus 29 infection increased with depletion of component Kayak and decreased with depletion of 30 negative regulator Puckered. Virus-induced JNK pathway regulates complement and 31 apoptosis in SGs via TEP20 and Dronc, respectively. Individual and co-silencing of these 32 genes demonstrate their antiviral effects and that both may function together. Co-silencing 33 either TEP20 or Dronc with Puckered annihilates JNK pathway antiviral effect. We 34 identified and characterized the broad antiviral function of JNK pathway in SGs, expanding 35 the immune arsenal that blocks arbovirus transmission. 36 37 38Despite the critical role of SGs in transmission, only three studies have examined DENV-87 responsive differential gene expression in SGs. These studies revealed activation of the Toll 88 5 and IMD pathways (Bonizzoni et al., 2012; Luplertlop et al., 2011; Sim et al., 2012) and 89 identified the anti-DENV functions of Cecropin (Luplertlop et al., 2011), putative Cystatin 90 and ankyrin-repeat proteins (Sim et al., 2012). Here, we characterized the SG immune 91 response to DENV, ZIKV and CHIKV. We performed the first high throughput RNA-92 sequencing (RNA-seq) in infected SGs and observed differentially expressed genes (DEGs) 93 related to immunity, apoptosis, blood-feeding and lipid metabolism. Using gene silencing, we 94 discovered that upregulated components of the Toll and IMD pathways had variable effects 95 against DENV, ZIKV and CHIKV. However, silencing of a JNK pathway upregulated 96 component increased, and silencing of a negative regulator decreased infection by the three 97 viruses in SGs. Further, we show that the JNK pathway is activated by all viruses and triggers 98 a cooperative complement and apoptosis response in SGs. This work identifies and 99 characterizes the JNK antiviral response that reduces DENV, ZIKV and CHIKV in A. aegypti 100 SGs. 101 102 Results 103 Transcriptome regulation by DENV, ZIKV and CHIKV in SGs 104 SGs were collected at 14 days post oral infection (dpi) with DENV and ZIKV, and at seven 105 dpi with CHIKV (Supplementary Figure 1) to account for variability between virus extrinsic 106 incubation periods (EIP) (Mbaika et al., 2016; Salazar et al., 2007). Differentially expressed 107 genes (DEGs) were calculated with DESeq2, edgeR and Cuffdiff 2, and showed little overlap 108 among the algorithms (Supplementary Figure 2). To validate DEGs and select which 109 software to use, we quantified the expression of 10 genes in a biological repeat with RT-1...

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“…We also notice the significant induction of caudal, and reduction of pgrps, pgrp-la, -lc, -ld, and the antimicrobial peptides, defensin in dsAsteglut1 mosquitoes, suggesting that Asteglut1 might be involved in the regulation of immune responses [25,40,56]. PGRP-LA is a receptor of mosquito immune deficiency pathway (Imd) [41]. It helps to control the homeostasis of gut microbiota and parasite infection in An.…”

Section: Discussionmentioning

confidence: 96%

“…Five immune related genes were differentially regulated. Caudal, the negative regulator of Imd pathway was significantly up-regulated [40], while the peptidoglycan recognition proteins, pgrp-la, -lc, -ld, and the antimicrobial peptides, defensin were significantly down-regulated [25,40,41,42,43].…”

Section: Transcriptional Analysis Of Asteglut1-knockdown Mosquitoesmentioning

confidence: 98%

Glucose transporter GLUT1 influences Plasmodium berghei infection in Anopheles stephensi

Wang

2020

Preprint

View full text Add to dashboard Cite

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.

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

Cited by 48 publications

References 26 publications

Glucose transporter GLUT1 influences Plasmodium berghei infection in Anopheles stephensi

Glucose transporter GLUT1 influences Plasmodium berghei infection in Anopheles stephensi

JNK pathway restricts DENV, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands

Glucose transporter GLUT1 influences Plasmodium berghei infection in Anopheles stephensi

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