Early intervention by flu border patrol prevents pulmonary infection

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Figure 1: T cells (yellow) surrounding influenza infected cells (red) in the nose

It has previously been established by the present researchers, and others, that resident memory CD8 T cells (Trms) located in the lungs provided very good protection against different strains of influenza infection. The difficulty is that such protection wanes over a period of time because the Trms populations did not persist within the microenvironment of the lung, for reasons that are not understood at present.

Looking at the problem from a different angle, the present authors looked at what would happen if the virus was intercepted in the nasal tissues.  Flu is transmitted by a droplet infection, so the virus particles are deposited in the nose and upper airways where the infection is initiated. From there the infection spreads to the lower respiratory tract. Preventing the infection from establishing in the upper respiratory tract because of the presence of local Trms, would prevent the infection spreading to the lungs.

cross section through nasal tissue

Figure 2: cross section through nasal tissue

The findings showed that in the mouse model, a population of resident memory T cells persists in the nasal tissues unlike those in the lung which decline.  But more importantly, these specific flu fighting Trms were very active in preventing infection from establishing in the nasal tissues, and its subsequent spread to the lungs. Effectively the influenza virus could be stopped “at the gates”.

This raises the exciting prospect of a “one-shot” flu vaccine that could be administered once and would provide life-long protection. The reason for this is that present vaccines are directed against external parts of the virus which can vary in structure. The Trms instead recognise internal components of the virus which are highly conserved and are not easily modified.

Future research will be to develop the best strategies for establishing flu fighting resident T cells in the nasal tissues with the ultimate goal of developing a new vaccine that provides long term protection against influenza.

Media release from Doherty Institute: "Flu 'border patrol' starts at the nose (PDF 318.3 KB)".
Acknowledgement: Elisabeth Lopez, Media Advisor, Doherty Institute, for permission to use their media release

Publication details: Pizzolla A,  Nguyen Thi HO,  Smith JM,  Brooks AG,  Kedzieska K,  Heath WR, Reading PC, Wakim LM. Resident memory CD8+ T cells in the upper respiratory tract prevent pulmonary influenza virus infection. Science Immunology 2017 June - http://immunology.sciencemag.org/lookup/doi/10.1126/sciimmunol.aam6970