Mosquito immune responses and compatibility between Plasmodium parasites and anopheline mosquitoes

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 29892, USA.
BMC Microbiology (Impact Factor: 2.73). 08/2009; 9(1):154. DOI: 10.1186/1471-2180-9-154
Source: PubMed


Functional screens based on dsRNA-mediated gene silencing identified several Anopheles gambiae genes that limit Plasmodium berghei infection. However, some of the genes identified in these screens have no effect on the human malaria parasite Plasmodium falciparum; raising the question of whether different mosquito effector genes mediate anti-parasitic responses to different Plasmodium species.
Four new An. gambiae (G3) genes were identified that, when silenced, have a different effect on P. berghei (Anka 2.34) and P. falciparum (3D7) infections. Orthologs of these genes, as well as LRIM1 and CTL4, were also silenced in An. stephensi (Nijmegen Sda500) females infected with P. yoelii (17XNL). For five of the six genes tested, silencing had the same effect on infection in the P. falciparum-An. gambiae and P. yoelii-An. stephensi parasite-vector combinations. Although silencing LRIM1 or CTL4 has no effect in An. stephensi females infected with P. yoelii, when An. gambiae is infected with the same parasite, silencing these genes has a dramatic effect. In An. gambiae (G3), TEP1, LRIM1 or LRIM2 silencing reverts lysis and melanization of P. yoelii, while CTL4 silencing enhances melanization.
There is a broad spectrum of compatibility, the extent to which the mosquito immune system limits infection, between different Plasmodium strains and particular mosquito strains that is mediated by TEP1/LRIM1 activation. The interactions between highly compatible animal models of malaria, such as P. yoelii (17XNL)-An. stephensi (Nijmegen Sda500), is more similar to that of P. falciparum (3D7)-An. gambiae (G3).

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    • "There are several advantages of using an animal model of malaria and many research groups worldwide have begun using murine Plasmodium-based experimental models to better understand the interaction between malaria parasites and vectors. Essentially, these models have been helpful in the evaluation of potential interventions for malaria control and to generate and test hypotheses about the biology of human malaria and drug tests (Killick-Kendrick 1978, Jaramillo-Gutierrez et al. 2009, Xu et al. 2013). P. berghei was first found in the gut and salivary glands of Anopheles dureni (its natural invertebrate host) in Central Africa. "
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    Memórias do Instituto Oswaldo Cruz 02/2015; DOI:10.1590/0074-02760140266 · 1.59 Impact Factor
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    • "These two mosquito species can be readily colonised and are susceptible to infection with several parasite species, such as murine malarias (P. berghei and P. yoelii) (Blandin et al. 2004, Jaramillo-Gutierrez et al. 2009) or human malaria gametocyte cultures (P. falciparum) (Luckhart et al. 1998, Dong et al. 2006, Garver et al. 2009); making them robust laboratory models to study the biology of malaria transmission. "
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    Memórias do Instituto Oswaldo Cruz 05/2014; DOI:10.1590/0074-0276130553 · 1.59 Impact Factor
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    • "stephensi (Hor) form a highly compatible vector-parasite pair in which the host immune system is no longer effective. Jaramillo-Gutierrez et al. [64] showed that silencing several genes involved in oxidative (OXR1 and GSTT1) or immune (LRIM1 and CTL4) responses had no effect on P. yoelii (17XNL) infection of An. stephensi (Nijmegen Sda500). In this study, nitroquine induced immune responses of An. stephensi (Hor) by unknown mechanism. "
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    ABSTRACT: Antimalarial drugs may impact mosquito's defense against Plasmodium parasites. Our previous study showed nitroquine significantly reduced infection of Anopheles stephensi by Plasmodium yoelii, but the underlying mechanism remains unclear. In order to understand how transmission capacity of An. stephensi was affected by nitroquine, we explored the transcriptome of adult females after different treatments, examined changes in gene expression profiles, and identified transcripts affected by the drug and parasite. We extended massively parallel sequencing and data analysis (including gene discovery, expression profiling, and function prediction) to An. stephensi before and after Plasmodium infection with or without nitroquine treatment. Using numbers of reads assembled into specific contigs to calculate relative abundances (RAs), we categorized the assembled contigs into four groups according to the differences in RA values infection induced, infection suppressed, drug induced, and drug suppressed. We found both nitroquine in the blood meal and Plasmodium infection altered transcription of mosquito genes implicated in diverse processes, including pathogen recognition, signal transduction, prophenoloxidase activation, cytoskeleton assembling, cell adhesion, and oxidative stress. The differential gene expression may have promoted certain defense responses of An. stephensi against the parasite and decreased its infectivity. Our study indicated that nitroquine may regulate several immune mechanisms at the level of gene transcription in the mosquito against Plasmodium infection. This highlights the need for better understanding of antimalarial drug's impact on parasite survival and transmission. In addition, our data largely enriched the existing sequence information of An. stephensi, an epidemiologically important vector species.
    PLoS ONE 02/2014; 9(2):e89473. DOI:10.1371/journal.pone.0089473 · 3.23 Impact Factor
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