Influenza A virus causes the flu, an upper respiratory tract infection (nose and throat) that can result in severe disease if the virus migrates down into the lower respiratory tract (lung). Pulmonary influenza infection results in the deposition of influenza-specific CD8+ tissue-resident memory T cells (Trm) in the lung – these cells play a pivotal role in the control of secondary infections with different influenza virus strains. It was unknown whether influenza-specific Trm are also deposited in the nasal tissue, their developmental requirements and their capacity to control secondary influenza virus infections. We set out to answer these questions.
Using a mouse model, we found that influenza virus-specific Trm developed in the nasal tissue following influenza infection. Interestingly, they differed from the lung Trm for their greater longevity and for their development requirement of tissue antigen and TGF-β signaling. Both lung and nose Trm produced pro-inflammatory cytokines directly ex vivo and after in vivo re-infection. The capacity of influenza-specific T cells to convert to Trm was different in two sites, indicating organ-specific selection processes.
Importantly, nasal influenza-specific Trm protected against a secondary influenza infection and strikingly, also prevented the migration of this secondary virus from the nose to the lung halting the development of severe pulmonary infection.
Overall, lung and nasal Trm have different longevity and developmental requirements, but similar functionality as cytokine production and protection from secondary virus. Deeper understanding of acquired memory in the nose, the gateway of influenza virus infection, will assist in the development of better vaccination regimes.