Critical mechanistic studies have been carried out using animal models of human disease, but there are many more that need to be performed, particularly those that can model the species differences in gene regulation between humans and rodents. Figures S1—S4 and Table S1: The SIRP family of receptors and immune regulation. The authors carried out similar studies focusing on AD, but also with the aim of characterizing CD and CDR expression in elderly human brains [ 19 ]. This article has been cited by other articles in PMC.

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Surface plasmon resonance experiments were performed using a BIAcore The results are typical of three experiments. CD CD molecule http: The immunoregulatory properties of CD became further apparent upon the identification of the CDR.

To test whether the differences in the RAW What is unusual about this interaction is that CD is wihdows widely on endothelial and epithelial cells, suggesting that immunological style synapses may be important in these types of interactions in addition to the well-characterized interactions between leukocytes.

We conclude that the rabbit poxvirus CDlike proteins cause immunomodulation without utilizing CDR. A critical function for CD in wincows immune homeostasis and the severity of influenza infection. Treatment also mildly reduced lesions in chronically infected mice, though this would need to be combined with another winddows to prove efficacious. Although it had been shown that IL-4 induces neuronal expression of CD in rodent neurons in culture [ 39 ], the authors could not observe this using ILtreated cultured human neurons [W alker DG et al.


Herpesviruses and poxvi-ruses are exceptionally skilled at avoiding or subverting host immune responses Table 5. Human herpesvirus 8 K14 protein mimics CD in down-regulating macrophage activation through CD receptor.

Rabbit CD200R binds host CD200 but not CD200-like proteins from poxviruses

Brown and as described in Akkaya et al. Is this the factor keeping microglia or perivascular macrophages in a resting, ramified or surveillance state, or at least in an alternatively activated state? CD is a broadly distributed membrane protein that can downregulate myeloid cell activity by interacting with an inhibitory receptor termed CDR Hoek et al.

These data also confirm that dopaminergic neuronal toxins have a mechanism of action, including the induction of inflammation and microglial activation [ 56 ]. In certain situations, the greatest threat to the host is the excessive inflammation seen in response to the infectious organism. Cerebrospinal fluid, in particular, represents a clean biofluid that could be a reservoir for released CD from neurons.

In these cases, the disruption of the CD In the absence of specific reagents for these proteins, surface expressions of rabbit CD and rabbit CDR were detected using fluorescent beads coated with rabbit CDR and rabbit CD respectively by flow cytometry Fig. As it appears that rodents and humans regulate the expression of these genes differently, there is also a critical need for the preparation of humanized transgenic mice engineered to express human CD or CDR under their native human gene promoters.

These data clearly provide rationale for further investigations of the manipulation of CD and the CDR in human neurological diseases.

Full length coding sequences of myxoma M Accession no: This drug could also be used to treat pathogenic infections that are impacted by CD The purpose of this review is to assess the data regarding the role of CD—CDR interactions in relation to the brain in order to determine if this could be a therapeutic target for human brain diseases with inflammatory components, and what additional studies are needed.


Both nomenclatures were used in some of the earlier papers. Disulfide bonds are represented as yellow sticks.

Structures of CD/CD Receptor Family and Implications for Topology, Regulation, and Evolution

Finally, using knockdown models, we showed that the inhibitory effect of M on RAW Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Members of the herpesviruses and poxviruses have incorporated or evolved orthologs of the host CD protein in their genome Table 5. In fact, when MCMV is continuously passaged in Ly49H positive cells in culture, the virus will quickly generate mutations in m to avoid binding to the activating receptor Voigt et al.

Implications for anti-CD therapy. Deckert, Sedgwick, Fischer, and Schluter These data suggest that many pathogens can take advantage of host inhibitory receptors to modulate inflammatory responses.

The CD200–CD200R1 Inhibitory Signaling Pathway: Immune Regulation and Host–Pathogen Interactions

Potential N-linked glycosylation sites are shown in pink. National Center for Biotechnology InformationU.

Gray shaded area refers to uninfected cells.