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| Status |
Public on Aug 10, 2013 |
| Title |
Bacteria- and IMD Pathway-Independent Immune Defenses against Plasmodium falciparum in Anopheles gambiae |
| Organism |
Anopheles gambiae |
| Experiment type |
Expression profiling by array
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| Summary |
The mosquito Anopheles gambiae uses its innate immune system to control bacterial and Plasmodium infection of its midgut tissue. The activation of potent IMD pathway-mediated anti-Plasmodium falciparum defenses is dependent on the presence of the midgut microbiota, which activate this defense system upon parasite infection through a peptidoglycan recognition protein, PGRPLC. We employed transcriptomic and reverse genetic analyses to compare the P. falciparum infection-responsive transcriptomes of septic and aseptic mosquitoes and to determine whether bacteria-independent anti-Plasmodium defenses exist. To examine the impact of P. falciparum infection on the mosquito midgut and carcass transcriptomes in the presence or absence of midgut bacteria, we used A. gambiae whole genome microarrays to compare the mRNA abundance of P. falciparum-infected and -naïve mosquitoes of antibiotic- and non-antibiotic treated cohorts. P. falciparum infection induced changes in the abundance of as many as 2,183 and 2,429 transcripts in whole mosquitoes belonging to a variety of functional groups in aseptic and septic mosquitoes. Ultimately, we were interested in identifying the genes involved in bacteria-independent anti-Plasmodium responses, and therefore we focused on transcripts displaying increased abundance in the parasite-infected aseptic midguts, placing a particular emphasis on those with predicted immune functions. Because of the central role of serine protease cascades in regulating insect immune defenses, we focused the remainder of our analysis on a clip-domain serine protease C2 (CLIPC2, AGAP004317) and a serine protease inhibitor 7 (SRPN7, AGAP007693) that were specifically upregulated in the parasite-infected, aseptic mosquito midgut. We showed that SRPN7 negatively and CLIPC2 positively regulate the anti-Plasmodium defense, independently of the midgut-associated bacteria. Co-silencing assays suggested that these two genes may function together in a signaling cascade. Neither gene was regulated, nor modulated, by infection with the rodent malaria parasite Plasmodium berghei, suggesting that SRPN7 and CLIPC2 are components of a defense system with preferential activity towards P. falciparum. Further analysis using RNA interference determined that these genes do not regulate the anti-Plasmodium defense mediated by the IMD pathway, and both factors act as agonists of the endogenous midgut microbiota, further demonstrating the lack of functional relatedness between these genes and the bacteria-dependent activation of the IMD pathway. This is the first study confirming the existence of a bacteria-independent, anti-P. falciparum defense.
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| Overall design |
Aseptic and septic midguts and carcasses from P. falciparum-infected A. gambiae vs aseptic and septic midguts and carcasses from uninfected, blood-fed A. gambiae. 3 biological replicates and 1 pseudo-replicate per each array.
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| Contributor(s) |
Blumberg BJ, Trop S, Das S, Dimopoulos G |
| Citation(s) |
24019865 |
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| Submission date |
Aug 09, 2013 |
| Last update date |
Nov 11, 2013 |
| Contact name |
George Dimopoulos |
| E-mail(s) |
gdimopo1@jhu.edu
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| Phone |
443 28 70128
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| Organization name |
Johns Hopkins School of Public Health
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| Department |
Molecular Microbiology and Immunology
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| Street address |
615 N. Wolfe Street
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21205 |
| Country |
USA |
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| Platforms (1) |
| GPL17550 |
Agilent-026185 AGTRAN2009 array |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA214747 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE49690.xlsx.gz |
867.5 Kb |
(ftp)(http) |
XLSX |
| GSE49690_RAW.tar |
57.2 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
| Processed data are available on Series record |
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