Immunological biomarkers in severe asthma Narendra, Dharani; Blixt, John; Hanania, Nicola A.
Seminars in immunology,
December 2019, 2019-12-00, 20191201, Letnik:
46
Journal Article
Recenzirano
•Asthma is a heterogeneous disease with several phenotypes and endotypes and Biomarkers help in the phenotyping and endotyping of asthma.•Biomarkers should be clinically applicable and act as ...surrogate markers to reflect disease mechanisms, predict the course of disease, and response to certain therapies.•Only few biomarkers that reflect T2 airway inflammation are currently readily available for clinical use.•There is a great unmet need for biomarkers reflecting T2-Low asthma.•Use of composite biomarkers may prove to be of greater importance than a single biomarkers but that needs further evaluation.
Severe asthma is heterogeneous in its clinical presentation, underlying pathophysiology, course and response to therapy. Clinical and physiological assessment of severe asthma is often inadequate in predicting underlying disease mechanisms and or response to medications. With the emergence of novel targeted therapies in severe asthma, the need for reproducible, easily measured biomarkers became obvious but only few are currently available for clinical use. These biomarkers along with the clinical presentation of the patient play an important role in identifying phenotypes and endotypes, predicting the clinical course and prognosis and improving the precision therapeutic approach to asthma.
The invasion of host cells by sporozoites of
Toxoplasma gondii leads to the formation of parasitophorous vacuoles that are distinctly different from those surrounding tachyzoites. In ...sporozoite-infected cells, the fluid-filled space surrounding the sporozoite is many times larger in volume than the sporozoite, essentially lacks granular or tubular structures, and has no detectable continuous parasitophorous vacuolar membrane when prepared by conventional electron microscopic methods. Consistent with the ultrastructural differences, dense-granule protein GRA3, which associates with the parasitophorous vacuolar membrane of tachyzoites, was not detected by indirect immunofluorescence in sporozoite-infected cells 2–12 h post-inoculation or by Western blot analysis of sporozoite extracts. Western blots incubated with theαROP/DG antiserum, which recognizes tachyzoite rhoptry and dense-granule proteins, revealed numerous other antigenic differences between sporozoites and tachyzoites. Cell cultures inoculated with sporozoites were monitored at various intervals for the expression of GRA3 and the developmentally-regulated tachyzoite surface protein SAG1. Expression of SAG1 and GRA3 was first observed in 30% of the sporozoite-infected cells at 12 and 15 h post-inoculation, respectively, and in all intracellular parasites at 24 h. Parasite replication was only observed in sporozoite-infected cells that were positive for GRA3 and SAG1. Thus, these data indicate that sporozoites and their interaction with host cells differ substantially from tachyzoites and the expression of tachyzoite-specific proteins is likely required for parasite replication.
Cryptosporidium parvum oocysts isolated from calf feces were examined by scanning electron microscopy during excystation. Intact C. parvum oocysts were spheroid to ellipsoid, approximately equal to ...3.5 X 4.0 micron, with length : width ratio = 1.17. The oocyst wall had a single suture at one pole, which spanned 1/3 to 1/2 the circumference of the oocyst. During excystation the suture dissolved, resulting in a slit-like opening, which the sporozoites used to exit the oocyst. Sporozoites were 3.8 X 0.6 micron and had a rough outer surface.
•Aged males had greater mortality than females despite equivalent stroke injury.•Systemic effects on gut permeability and microbiota diversity were larger in males.•Brain T cell immune responses were ...temporally distinct and more pronounced in males.•Sensorimotor deficits were greater in aged males than in females.
Stroke is a disease that presents with well-known sex differences. While women account for more stroke deaths, recent data show that after adjusting for age and pre-stroke functional status, mortality is higher in men. Immune responses are key determinants of stroke outcome and may differ by sex. This study examined sex differences in central and peripheral T cell immune responses, systemic effects on gut permeability and microbiota diversity and behavioral outcomes after stroke in aged mice. We hypothesized that there are sex differences in the immune response to stroke in aged animals.
C57BL/6CR mice (20–22 months) were subjected to 60 min middle cerebral artery occlusion, or sham surgery. T cells were quantified in brain and blood at 3, 7 and 15 days (d) post-stroke by flow cytometry. Peripheral effects on gut permeability and microbiota diversity, as well as neurological function were assessed up to 14 d, and at 21 d (cognitive function) post-stroke. Brain glial fibrillary acidic protein (GFAP) expression was evaluated at 42 d post-stroke.
Mortality (50% vs 14%, p < 0.05) and hemorrhagic transformation (44% vs 0%) were significantly higher in males than in females. No difference in infarct size at 3d were observed. Peripherally, stroke induced greater gut permeability of FITC-dextran in males at d3 (p < 0.05), and non-reversible alterations in microbiota diversity in males. Following the sub-acute phase, both sexes demonstrated a time-dependent increase of CD4+ and CD8+ T cells in the brain, with significantly higher levels of CD8+ T cells and Regulatory T cells in males at d15 (p < 0.01). Aged males demonstrated greater neurological deficits up to d5 and impaired sensorimotor function up to d15 when assessed by the corner asymmetry test (p < 0.001 and p < 0.01, respectively). A trend in greater cognitive decline was observed at d21 in males. Increased GFAP expression in the ischemic hemisphere, indicating astroglial activation and gliosis, was demonstrated in both males and females 42d post-stroke. Our findings indicate that despite a similar initial ischemic brain injury, aged male mice experience greater peripheral effects on the gut and ongoing central neuroinflammation past the sub-acute phase after stroke.
Here we describe a glycan microarray constructed by using standard robotic microarray printing technology to couple amine functionalized glycans to an amino-reactive glass slide. The array comprises ...200 synthetic and natural glycan sequences representing major glycan structures of glycoproteins and glycolipids. The array has remarkable utility for profiling the specificity of a diverse range of glycan binding proteins, including C-type lectins, siglecs, galectins, anticarbohydrate antibodies, lectins from plants and microbes, and intact viruses.
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