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The endosymbiotic bacterium  Wolbachia  is being investigated as a potential control agent in several important vector insect species. Recent studies have shown that  Wolbachia  can protect the insect host against a wide variety of pathogens, resulting in reduced transmission of parasites and viruses. It has been proposed that compromised vector competence of  Wolbachia -infected insects is due to up-regulation of the host innate immune system or metabolic competition.  Anopheles  mosquitoes, which transmit human malaria parasites, have never been found to harbor  Wolbachia  in nature. While transient somatic infections can be established in  Anopheles , no stable artificially-transinfected  Anopheles  line has been developed despite numerous attempts. However, cultured  Anopheles  cells can be stably infected with multiple  Wolbachia  strains such as wAlbB from  Aedes albopictus , wRi from  Drosophila simulans  and wMelPop from  Drosophila melanogaster . Infected cell lines provide an amenable system to investigate  Wolbachia - Anopheles  interactions in the absence of an infected mosquito strain. We used Affymetrix GeneChip microarrays to investigate the effect of wAlbB and wRi infection on the transcriptome of cultured  Anopheles  Sua5B cells, and for a subset of genes used quantitative PCR to validate results in somatically-infected  Anopheles  mosquitoes.  Wolbachia  infection had a dramatic strain-specific effect on gene expression in this cell line, with almost 700 genes in total regulated representing a diverse array of functional classes. Very strikingly, infection resulted in a significant down-regulation of many immune, stress and detoxification-related transcripts. This is in stark contrast to the induction of immune genes observed in other insect hosts. We also identified genes that may be potentially involved in  Wolbachia -induced reproductive and pathogenic phenotypes. Somatically-infected mosquitoes had similar responses to cultured cells. The data show that  Wolbachia  has a profound and unique effect on  Anopheles  gene expression in cultured cells, and has important implications for mechanistic understanding of  Wolbachia -induced phenotypes and potential novel strategies to control malaria.

Wolbachia Infections in Anopheles gambiae Cells: Transcriptomic Characterization of a Novel Host-Symbiont Interaction