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Immunology - Infectious Diseases - Respiratory Medicine

Protective Role of P2Y2 Receptor against Lung Infection Induced by Pneumonia Virus of Mice
Published: Wednesday, November 21, 2012
Author: Gilles Vanderstocken et al.

by Gilles Vanderstocken, Els Van de Paar, Bernard Robaye, Larissa di Pietrantonio, Benjamin Bondue, Jean-Marie Boeynaems, Daniel Desmecht, Didier Communi

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-3a 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.