3 research outputs found
Systems Biology of Tissue-Specific Response to Anaplasma phagocytophilum Reveals Differentiated Apoptosis in the Tick Vector Ixodes scapularis
Anaplasma phagocytophilum is an emerging pathogen that causes human
granulocytic anaplasmosis. Infection with this zoonotic pathogen affects
cell function in both vertebrate host and the tick vector, Ixodes
scapularis. Global tissue-specific response and apoptosis signaling
pathways were characterized in I. scapularis nymphs and adult female
midguts and salivary glands infected with A. phagocytophilum using a
systems biology approach combining transcriptomics and proteomics.
Apoptosis was selected for pathway-focused analysis due to its role in
bacterial infection of tick cells. The results showed tissue-specific
differences in tick response to infection and revealed differentiated
regulation of apoptosis pathways. The impact of bacterial infection was
more pronounced in tick nymphs and midguts than in salivary glands,
probably reflecting bacterial developmental cycle. All apoptosis
pathways described in other organisms were identified in I. scapularis,
except for the absence of the Perforin ortholog. Functional
characterization using RNA interference showed that Porin knockdown
significantly increases tick colonization by A. phagocytophilum.
Infection with A. phagocytophilum produced complex tissue-specific
alterations in transcript and protein levels. In tick nymphs, the
results suggested a possible effect of bacterial infection on the
inhibition of tick immune response. In tick midguts, the results
suggested that A. phagocytophilum infection inhibited cell apoptosis to
facilitate and establish infection through up-regulation of the JAK/STAT
pathway. Bacterial infection inhibited the intrinsic apoptosis pathway
in tick salivary glands by down-regulating Porin expression that
resulted in the inhibition of Cytochrome c release as the anti-apoptotic
mechanism to facilitate bacterial infection. However, tick salivary
glands may promote apoptosis to limit bacterial infection through
induction of the extrinsic apoptosis pathway. These dynamic changes in
response to A. phagocytophilum in I. scapularis tissue-specific
transcriptome and proteome demonstrated the complexity of the tick
response to infection and will contribute to characterize gene
regulation in ticks.This research was supported by grants BFU2011-23896, the EU FP7 ANTIGONE
project number 278976, the Oklahoma Agricultural Experiment Grant 1669
and the Walter R. Sitlington Endowed Chair for Food Animal Research to
KMK. NA and RCG were funded by MEC, Spain. RS was supported by the
project Postdok\_BIOGLOBE (CZ.1.07/2.3.00/30.0032) and the Grant
13-12816P (GA CR). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.S
Systems Biology of Tissue-Specific Response to <i>Anaplasma phagocytophilum</i> Reveals Differentiated Apoptosis in the Tick Vector <i>Ixodes scapularis</i>
<div><p><i>Anaplasma phagocytophilum</i> is an emerging pathogen that causes human granulocytic anaplasmosis. Infection with this zoonotic pathogen affects cell function in both vertebrate host and the tick vector, <i>Ixodes scapularis</i>. Global tissue-specific response and apoptosis signaling pathways were characterized in <i>I</i>. <i>scapularis</i> nymphs and adult female midguts and salivary glands infected with <i>A</i>. <i>phagocytophilum</i> using a systems biology approach combining transcriptomics and proteomics. Apoptosis was selected for pathway-focused analysis due to its role in bacterial infection of tick cells. The results showed tissue-specific differences in tick response to infection and revealed differentiated regulation of apoptosis pathways. The impact of bacterial infection was more pronounced in tick nymphs and midguts than in salivary glands, probably reflecting bacterial developmental cycle. All apoptosis pathways described in other organisms were identified in <i>I</i>. <i>scapularis</i>, except for the absence of the Perforin ortholog. Functional characterization using RNA interference showed that Porin knockdown significantly increases tick colonization by <i>A</i>. <i>phagocytophilum</i>. Infection with <i>A</i>. <i>phagocytophilum</i> produced complex tissue-specific alterations in transcript and protein levels. In tick nymphs, the results suggested a possible effect of bacterial infection on the inhibition of tick immune response. In tick midguts, the results suggested that <i>A</i>. <i>phagocytophilum</i> infection inhibited cell apoptosis to facilitate and establish infection through up-regulation of the JAK/STAT pathway. Bacterial infection inhibited the intrinsic apoptosis pathway in tick salivary glands by down-regulating Porin expression that resulted in the inhibition of Cytochrome c release as the anti-apoptotic mechanism to facilitate bacterial infection. However, tick salivary glands may promote apoptosis to limit bacterial infection through induction of the extrinsic apoptosis pathway. These dynamic changes in response to <i>A</i>. <i>phagocytophilum</i> in <i>I</i>. <i>scapularis</i> tissue-specific transcriptome and proteome demonstrated the complexity of the tick response to infection and will contribute to characterize gene regulation in ticks.</p></div