Identification of SIGN-R1 as responsible of influenza virus recognition
on Monday, July 29, 2019
A team of researchers from the Institute for Research in Biomedicine (IRB, affiliated to USI Università della Svizzera italiana, Switzerland) have discovered and identified a molecule – SIGN-R1 – capable of recognizing the multiple variants of influenza and consequently 'directing' the immune response in individuals affected by the disease. The results of the research, which pave the way for the design of alternative therapies to vaccination, are published in the scientific journal Nature Microbiology.
Influenza is one of the most common diseases responsible of multiple hospitalizations worldwide, especially in elder and immunocompromised people. However, despite the development of effective influenza vaccines, the virus is able to mutate and escape the body defences. Therefore, to protect against influenza, an annual reformulation of the vaccine is required. In later years, the scientists have focused on studying alternative ways to neutralize completely the virus that would not require annual revaccination.
The research team at IRB in Bellinzona, Switzerland, led by Dr. Santiago González, has identified a molecule, expressed by the cells of the immune system responsible of detecting the virus and alerting the host defences. This molecule, named SIGN-R1, is able to recognize multiple variants of influenza virus. After recognition of the virus, SIGN-R1 directs the immune response to eliminate the virus. Interestingly, SIGN-R1 is also able to bind to other important respiratory pathogens such as Streptococcus pneumoniae.
The research results open the way to design alternative therapies to vaccination against respiratory pathogens, including influenza virus, based on the use of new molecules from the same family as SIGN-R1. The potential treatments based on this molecules might be used in all the clinical cases in which patients are already infected, in which vaccination is not efficient, or in those cases in which vaccines are not very effective (elderly and children) to improve the effect of the vaccine.
“The fact that SIGN-R1, a molecule that is already present in the host, has the ability to bind so efficiently different subtypes of influenza virus represents a surprising and an innovative start point for the development of new therapies against influenza” said Miguel Palomino-Segura, PhD, main author of this publication that was mainly developed during his doctoral studies at the program of Immunology from the University of Bern.
|After infection of the epithelial cells that coat the inner part of the trachea, the immune cells (yellow) recognize influenza virus (red) thanks to the molecule SIGN-R1 (orange). The immune cell produce molecules that alert the immune system and promote the recruitment of killer cells (pink), that will attack the infected cells and break the cycle of replication of the virus.|
|3D reconstruction of microscopy images showing the binding (indicated by white arrows) of influenza virus (green) to SIGN-R1 (red) expressed in the surface of an immune cell from the trachea.|
This work was possible thanks to funding from the Swiss National Science Foundation, the European Union (Marie Curie Action Career Integration Grant) and the SystemsX.ch initiative, and represents a collaboration between four international institutions including Harvard Medical School (Boston, USA), Mount Sinai School of Medicine (New York, USA), University of Toulouse (Toulouse, France), and the IRB (Bellinzona, Switzerland).
Protection against influenza infection requires early recognition by inflammatory dendritic cells through C-type lectin receptor SIGN-R1.
Palomino-Segura M. , Perez L. , Farsakoglu Y. , Virgilio T., Latino I. , D’Antuono R. , Chatziandreou N., Pizzagalli D. U. , Wang G. , García-Sastre A. , Sallusto F. , Carroll M. C. , Neyrolles O. and Gonzalez S. Nature Microbiology, 2019, https://www.nature.com/articles/s41564-019-0506-6