Future treatments may involve customizing treatment to the virus pathotype.

ATP released in the early inflammatory processes acts as a danger signal by binding to purinergic receptors expressed on immune cells. A major contribution of the P2Y2 receptor of ATP/UTP to dendritic cell function and Th2 lymphocyte recruitment during asthmatic airway inflammation was previously reported. We investigated here the involvement of P2Y2 receptor in lung inflammation initiated by pneumonia virus of mice infection. We demonstrated that P2Y2 −/− mice display a severe increase in morbidity and mortality rate in response to the virus. Lower survival of P2Y2 −/− mice was not significantly correlated with excessive inflammation despite the higher level of neutrophil recruiters in their bronchoalveolar fluids. Interestingly, we observed reduced ATP level and lower numbers of dendritic cells, CD4+ T cells and CD8+ T cells in P2Y2 −/− compared to P2Y2 +/+ infected lungs. Lower level of IL-12 and higher level of IL-6 in bronchoalveolar fluid support an inhibition of Th1 response in P2Y2 −/− infected mice. Quantification of DC recruiter expression revealed comparable IP-10 and MIP-3α levels but a reduced BRAK level in P2Y2 −/− compared to P2Y2 +/+ bronchoalveolar fluids. The increased morbidity and mortality of P2Y2 −/− mice could be the consequence of a lower viral clearance leading to a more persistent viral load correlated with the observed higher viral titer. The decreased viral clearance could result from the defective Th1 response to PVM with a lack of DC and T cell infiltration. In conclusion, P2Y2 receptor, previously described as a target in cystic fibrosis therapy and as a mediator of Th2 response in asthma, may also regulate Th1 response protecting mice against lung viral infection.

Influenza A virus remains a major public health problem. Mouse models have been widely used to study influenza infection in mammals. DBA/2J and C57BL/6J represent extremes in terms of susceptibility to influenza A infection among inbred laboratory mouse strains. Several studies focused specifically on the factors responsible for the susceptibility of DBA/2J or the resistance of C57BL/6J and resulted in impressive lists of candidate genes or factors over- or underexpressed in one of the strains. We adopted a different phenotypical approach to identify the critical steps of the infection process accounting for the differences between DBA/2J and C57BL/6J strains. We concluded that both a dysfunction of alveolar macrophages and an increased permissivity of respiratory cells rendered DBA/2J more susceptible to influenza infection.

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