A Molecular Camouflage to Evade Innate Immunity

Innate immunity is the first line of defense employed by our body to fight against pathogens in general. Phagocytic killing of pathogens is an important aspect of innate immunity. The phagocytic cells of the innate immune mechanism such as the neutrophils and macrophages, are capable of discriminating between self and non-self and selectively kill the foreign (non-self) pathogens.

How do phagocytic cells do not kill our own cells?

All our cells have a glycoprotein attached to our cell membrane that is designated as CD47. Macrophages have a receptor for CD47, called as SIRPα (Signal Regulatory Protein-Alpha). Binding of a CD47 on our cell surface to the receptor SIRPα present on a phagocytic cell, prevents the phagocytes from the phagocytic killing of such cells.

CD47
http://www.rcsb.org/pdb/explore/explore.do?structureId=2jjs

Thus CD47 molecule provides a “self” signal to phagocytes and spares cells carrying this signal molecule from being destructed by phagocytes. The gene for this CD47 is located in the long arm of Chromosome number 3 (3q13.1-q13.2).

In essence, any foreign particle or cell tagged with the CD47 peptide act as a passport, stay in the body without triggering any inflammatory responses and evade from being destructed by phagocytic cells of the innate immune system.

Dennis Discher from the Molecular and Cell Biophysics and NanoBioPolymers Laboratory (University of Pennsylvania, Philadelphia) and associates, made use of this idea. They chemically synthesized a peptide similar to but smaller than CD47. This synthetic peptide with only 21 aminoacid residues can exactly fall into the groove of the (CD47 receptor) SIRPα and thus can prevent an inflammatory response. The researchers attached these ‘molecular mimic’ of the ‘self-peptide’ (CD47 mimic) to nanobeads and then injected them into hosts and successfully found out that such tagged nanobeads were indeed recognized as ‘self structures’ and phagocytic cells spared them from destruction!

In future, this ‘immune-evading’ strategy could help in the diagnosis and therapy of cancers.

-      Dr. P. Kumarasamy

Further Reading:

http://www.sciencemag.org/content/339/6122/971.abstract

http://blogs.nature.com/spoonful/2013/02/nanoparticles-engineered-to-shuttle-cancer-drug-past-immune-system.html

http://www.youtube.com/watch?v=dmaeaS6uRLA
http://cen.acs.org/articles/91/i8/Peptide-Fools-Immune-System-Allowing.html