These observations led us to wonder how Wolbachia is detected Microbiology inhibitor within the cell, how Wolbachia evades the host immune system, and what are the consequences of these manipulations on host cell physiology. In the present study, most of the canonical immune PGRP receptors were differentially-regulated in the presence of Wolbachia, probably through lipoprotein or polysaccharide binding, and the outcome of the interaction tended towards under-expression of immune effectors of the Toll, Imd and JAK-STAT pathways. Even when the regulation

cascade was too complex to analyze, the expression patterns of most immune genes were modified in response to symbiosis, suggesting that Wolbachia may adopt an active strategy of immune evasion in A. tabida. However, as few immune genes from the AICAR Toll signaling pathway are also known to play a role in development, expression data have to be interpreted with caution with respect to the important development defect of ovaries in aposymbiotic females. The regulation appeared to be tissue or sex-specific, immune genes being expressed to a greater extent

in males than in ovarian tissues. Wolbachia is mainly concentrated in the ovaries of females, whereas they are spread more widely throughout the male body [61]. Hence, modulation of immune pathways could be both gene- and tissue-specific, as shown in the differential immune regulation of bacteriocytes vs. whole body in Sitophilus zeamais [62]. The immune response to Wolbachia also seems to be host strain-specific, with the Pi3 strain generally exhibiting a more pronounced pattern than the NA strain. Finally, the immune response to Wolbachia seems to be host-specific, as Drosophila simulans did

not repress or induce antimicrobial peptides production [63], whereas the D. melanogaster cell line over-expressed antimicrobial peptides in response to Wolbachia infection [23]. Similarly, the presence of Wolbachia tends to increase immune gene expression in the mosquito hosts when stably introduced [20, 21, 50]. By comparing aposymbiotic and symbiotic tissues of A. tabida, we also highlighted the influence of Wolbachia Buspirone HCl on host immunity in its broad sense, and especially on the regulation of cell homeostasis and the oxidative environment, which are known to play a key role in physiological responses to invasion by pathogens. Indeed, processes involved in the AG-120 in vivo control of the oxidative environment were highlighted both in in silico and in vitro subtractions, and confirmed by qRT-PCR. Given these observations, we further demonstrated the influence of Wolbachia on iron homeostasis and oxidative stress regulation in A. tabida [8, 14]. We confirmed the differential expression of Ferritin, a protein involved in iron storage and transport, in males, females and ovaries from the Pi strain [14].