Protective Role of P2Y2 Receptor against Lung Infection Induced by Pneumonia Virus of Mice

被引:24
作者
Vanderstocken, Gilles [1 ]
Van de Paar, Els [2 ]
Robaye, Bernard [3 ]
di Pietrantonio, Larissa [1 ]
Bondue, Benjamin [1 ,4 ]
Boeynaems, Jean-Marie [1 ,5 ]
Desmecht, Daniel [2 ]
Communi, Didier [1 ]
机构
[1] Univ Libre Bruxelles, IRIBHM, Inst Interdisciplinary Res, Brussels, Belgium
[2] Univ Liege, Dept Pathol, Fac Med Vet, Liege, Belgium
[3] Univ Libre Bruxelles, IRIBHM, Inst Interdisciplinary Res, Gosselies, Belgium
[4] Univ Libre Bruxelles, Erasme Hosp, Dept Pneumol, Brussels, Belgium
[5] Univ Libre Bruxelles, Erasme Hosp, Dept Lab Med, Brussels, Belgium
来源
PLOS ONE | 2012年 / 7卷 / 11期
关键词
DENDRITIC CELLS; EXPRESSION; PNEUMOVIRUS; BRAK/CXCL14; TISSUE; MODEL; BRAK;
D O I
10.1371/journal.pone.0050385
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-3 alpha 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.
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页数:6
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