The sandfly Lutzomyia longipalpis LL5 embryonic cell line has active Toll and Imd pathways and shows immune responses to bacteria, yeast and Leishmania

Tinoco-Nunes, Bruno; Telleria, Erich Loza; Silva-Neves, Monique da; Marques, Carla; Azevedo-Brito, Daisy Aline; Pitaluga, André Nóbrega; Traub-Csekö, Yara M.

doi:10.1186/s13071-016-1507-4

Cited by 34 publications

(46 citation statements)

References 39 publications

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“…Roles for insect immunity in controlling their transmission of infectious pathogens have been reported previously, including transmission of dengue virus by Aedes aegypti mosquitos (5)(6)(7), of African trypanosomes by the tsetse fly Glossina morsitans (8), and of malaria parasites by Anopheles gambiae (9,10). Concerning sand flies, a previous study showed that both the Toll and IMD pathways are activated by yeast, bacteria, and Leishmania in cultured Lutzomyia longipalpis sand fly cells (11). A defensin AMP was produced in Phlebotomus duboscqi flies after challenge by injected bacteria or feeding with bacteria or L. major and also presented an antiparasitic action in vitro (12).…”

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confidence: 74%

“…Finally, while our CRISPR strategy focused only the IMD pathway, other pathways are of crucial importance in the insect immune response (3,4). A role for the Toll pathway seems especially likely in the sand fly response to Leishmania because, as with the IMD pathway, its activation was observed in vitro when cultured sand fly cells were exposed to bacteria or Leishmania (11), and upregulation of a gene encoding a defensin AMP, whose expression in Drosophila depends on Toll (3), was observed in flies infected with L. major (12,13).…”

Section: Discussionmentioning

confidence: 99%

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CRISPR/Cas9 Mutagenesis in Phlebotomus papatasi: the Immune Deficiency Pathway Impacts Vector Competence for Leishmania major

Louradour

Ghosh

Inbar

et al. 2019

mBio

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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.

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confidence: 74%

Section: Discussionmentioning

confidence: 99%

CRISPR/Cas9 Mutagenesis in Phlebotomus papatasi: the Immune Deficiency Pathway Impacts Vector Competence for Leishmania major

Louradour

Ghosh

Inbar

et al. 2019

mBio

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“…In the case of L. longipalpis , previous studies utilizing cell lines focused on the interaction of these cells with Leishmania (Rey et al , 2000 ; Cortes et al , 2011 ). Our group has investigated the response of LL5 cells to various organisms including viruses (Pitaluga et al , 2008 ) as well as yeast, Leishmania and bacteria (Tinoco-Nunes et al , 2016 ). LL5 challenges with the Gram− Staphylococcus aureus and the Gram+ Escherichia coli and S. marcescens activated the Toll and IMD pathways, with S. aureus and S. marcescens triggering an early response (Tinoco-Nunes et al , 2016 ).…”

Section: Sand Flies and Bacteria: Interdependence And Immune Responsementioning

confidence: 99%

Leishmania, microbiota and sand fly immunity

et al. 2018

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In this review, we explore the state-of-the-art of sand fly relationships with microbiota, viruses and Leishmania, with particular emphasis on the vector immune responses. Insect-borne diseases are a major public health problem in the world. Phlebotomine sand flies are proven vectors of several aetiological agents including viruses, bacteria and the trypanosomatid Leishmania, which are responsible for diseases such as viral encephalitis, bartonellosis and leishmaniasis, respectively. All metazoans in nature coexist intimately with a community of commensal microorganisms known as microbiota. The microbiota has a fundamental role in the induction, maturation and function of the host immune system, which can modulate host protection from pathogens and infectious diseases. We briefly review viruses of public health importance present in sand flies and revisit studies done on bacterial and fungal gut contents of these vectors. We bring this information into the context of sand fly development and immune responses. We highlight the immunity mechanisms that the insect utilizes to survive the potential threats involved in these interactions and discuss the recently discovered complex interactions among microbiota, sand fly, Leishmania and virus. Additionally, some of the alternative control strategies that could benefit from the current knowledge are considered.

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“…Both pathways have been shown to play a role in the response to trypanosomatids 13,[34][35][36][37][38] . Furthermore, we also investigated members of the Dual-oxidase (DUOX) and JAK-STAT pathways, both of which were implicated in D. melanogaster-H. muscarum interaction 13 .…”

Section: Differential Expression Associated With Trypanosomatid Presementioning

confidence: 99%

The Phlebotomus Papatasi Transcriptomic Response to Trypanosomatid-contaminated Blood is Robust but non-specific

Sloan

Sádlová

Leštinová

et al. 2020

Preprint

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Background Leishmaniasis, caused by parasites of the genus Leishmania, is a disease that effects up to 8 million people worldwide. Parasites are transmitted to human and animal hosts through the bite of an infected sand fly. Novel strategies for disease control, require a better understanding of the key step for transmission namely, the establishment of infection inside the fly.Methods In this work we wanted to identify fly transcriptomic signatures associated with infected blood meal with non-infected blood meal as our baseline. We used next generation sequencing to describe the transcriptome of the sand fly Phlebotomus papatasi when fed with blood alone or with blood containing one of three trypanosomatids: Leishmania major, Leishmania donovani and Herpetomonas muscarum: a parasite not transmitted to humans.Results Of these, only L. major was able to successfully establish an infection in P. papatasi. However, the transcriptional signatures observed were not specific to success or failure of infection but a generalised response to the blood meal.Conclusions This implies that sand flies perceive Leishmania as just one feature of their microbiome landscape and that any strategy to tackle transmission should focus on the response towards the blood meal rather than parasite establishment. This result will generate new thinking around the concept of stopping transmission by controlling the parasite inside the insect.

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The sandfly Lutzomyia longipalpis LL5 embryonic cell line has active Toll and Imd pathways and shows immune responses to bacteria, yeast and Leishmania

Cited by 34 publications

References 39 publications

CRISPR/Cas9 Mutagenesis in Phlebotomus papatasi: the Immune Deficiency Pathway Impacts Vector Competence for Leishmania major

CRISPR/Cas9 Mutagenesis in Phlebotomus papatasi: the Immune Deficiency Pathway Impacts Vector Competence for Leishmania major

Leishmania, microbiota and sand fly immunity

The Phlebotomus Papatasi Transcriptomic Response to Trypanosomatid-contaminated Blood is Robust but non-specific

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