title: Protective role of P2Y2 receptor against lung infection induced by pneumonia virus of mice.
abstract: 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 P2Y(2) 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 P2Y(2) receptor in lung inflammation initiated by pneumonia virus of mice infection. We demonstrated that P2Y(2) (-/-) mice display a severe increase in morbidity and mortality rate in response to the virus. Lower survival of P2Y(2) (-/-) 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 P2Y(2) (-/-) compared to P2Y(2) (+/+) infected lungs. Lower level of IL-12 and higher level of IL-6 in bronchoalveolar fluid support an inhibition of Th1 response in P2Y(2) (-/-) infected mice. Quantification of DC recruiter expression revealed comparable IP-10 and MIP-3α levels but a reduced BRAK level in P2Y(2) (-/-) compared to P2Y(2) (+/+) bronchoalveolar fluids. The increased morbidity and mortality of P2Y(2) (-/-) 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, P2Y(2) 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.
authors.affiliation: The Institute of Interdisciplinary Research, IRIBHM, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Gilles
authors.initials: G
authors.lastname: Vanderstocken
authors.forename: Els
authors.initials: E
authors.lastname: Van de Paar
authors.forename: Bernard
authors.initials: B
authors.lastname: Robaye
authors.forename: Larissa
authors.initials: L
authors.lastname: di Pietrantonio
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bondue
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Boeynaems
authors.forename: Daniel
authors.initials: D
authors.lastname: Desmecht
authors.forename: Didier
authors.initials: D
authors.lastname: Communi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D054418:Chemokine CCL20 / Q000235:genetics / Q000276:immunology; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005260:Female; D015870:Gene Expression; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D029122:Murine pneumonia virus / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000821:virology; D011024:Pneumonia, Viral / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D018186:Pneumovirus Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D058473:Receptors, Purinergic P2Y2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015996:Survival Rate; D018417:Th1 Cells / Q000276:immunology / Q000821:virology; D018418:Th2 Cells / Q000276:immunology / Q000821:virology
chemical_list: C517518:CXCL14 protein, mouse; D054418:Chemokine CCL20; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; D015850:Interleukin-6; D058473:Receptors, Purinergic P2Y2; D018664:Interleukin-12; D000255:Adenosine Triphosphate