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1.  Cytosolic surveillance and antiviral immunity 
Current opinion in virology  2011;1(6):455-462.
Innate immune surveillance mechanisms lie at the heart of the antiviral response. A growing number of germ-line encoded pattern recognition receptors have been identified which protect the host from infection by sensing the presence of viral molecules and inducing antiviral defenses. Most compartments that viruses gain access to are under active surveillance by one or more pattern recognition receptors. Members of the Toll-like receptor family guard the extracellular milieu and endosomal compartment where they are activated by viral glycoproteins or nucleic acids, respectively. More recently, the cytosolic compartment has emerged as the frontline in the arsenal of the host’s antiviral defenses. Families of receptors in the cytosol recognize viral RNA or DNA or perturbations of cellular homeostasis and orchestrate effector responses to eliminate the invader. Here, we review this expanding area of innate immunity by focusing on the molecular mechanisms of cytosolic host-defenses.
doi:10.1016/j.coviro.2011.11.004
PMCID: PMC3610561  PMID: 22440909
2.  Autophagy proteins regulate innate immune response by inhibiting NALP3 inflammasome-mediated mitochondrial DNA release 
Nature immunology  2010;12(3):222-230.
Autophagy, a cellular process for organelle and protein turnover, regulates innate immune responses. We demonstrate that depletion of autophagic proteins microtubule associated protein-1 light chain 3B (LC3B) and Beclin 1 enhances caspase-1 activation and secretion of interleukin-1β and interleukin-18. Autophagic protein depletion promoted accumulation of dysfunctional mitochondria and cytosolic translocation of mitochondrial DNA (mtDNA) in response to lipopolysaccharide (LPS) and ATP in macrophages. Release of mtDNA into the cytosol depended on the NALP3 inflammasome and mitochondrial ROS. Cytosolic mtDNA contributed to IL-1β and IL-18 secretion in response to LPS and ATP. LC3B-deficient mice produced more caspase-1-dependent cytokines in two sepsis models and were susceptible to LPS-induced mortality. Our study suggests that autophagic proteins regulate NALP3-dependent inflammation by preserving mitochondrial integrity.
doi:10.1038/ni.1980
PMCID: PMC3079381  PMID: 21151103
3.  Multiple factors interact to produce responses resembling spectrum of human disease in Campylobacter jejuni infected C57BL/6 IL-10-/- mice 
BMC Microbiology  2009;9:57.
Background
Campylobacter jejuni infection produces a spectrum of clinical presentations in humans – including asymptomatic carriage, watery diarrhea, and bloody diarrhea – and has been epidemiologically associated with subsequent autoimmune neuropathies. This microorganism is genetically variable and possesses genetic mechanisms that may contribute to variability in nature. However, relationships between genetic variation in the pathogen and variation in disease manifestation in the host are not understood. We took a comparative experimental approach to explore differences among different C. jejuni strains and studied the effect of diet on disease manifestation in an interleukin-10 deficient mouse model.
Results
In the comparative study, C57BL/6 interleukin-10-/- mice were infected with seven genetically distinct C. jejuni strains. Four strains colonized the mice and caused disease; one colonized with no disease; two did not colonize. A DNA:DNA microarray comparison of the strain that colonized mice without disease to C. jejuni 11168 that caused disease revealed that putative virulence determinants, including loci encoding surface structures known to be involved in C. jejuni pathogenesis, differed from or were absent in the strain that did not cause disease. In the experimental study, the five colonizing strains were passaged four times in mice. For three strains, serial passage produced increased incidence and degree of pathology and decreased time to develop pathology; disease shifted from watery to bloody diarrhea. Mice kept on an ~6% fat diet or switched from an ~12% fat diet to an ~6% fat diet just before infection with a non-adapted strain also exhibited increased incidence and severity of disease and decreased time to develop disease, although the effects of diet were only statistically significant in one experiment.
Conclusion
C. jejuni strain genetic background and adaptation of the strain to the host by serial passage contribute to differences in disease manifestations of C. jejuni infection in C57BL/6 IL-10-/- mice; differences in environmental factors such as diet may also affect disease manifestation. These results in mice reflect the spectrum of clinical presentations of C. jejuni gastroenteritis in humans and contribute to usefulness of the model in studying human disease.
doi:10.1186/1471-2180-9-57
PMCID: PMC2669091  PMID: 19296832

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