Author: Ullah, Md Ashik; Rittchen, Sonja; Li, Jia; Hasnain, Sumaira Z.; Phipps, Simon
Title: DP1 prostanoid receptor activation increases the severity of an acute lower respiratory viral infection in mice via TNF-α-induced immunopathology Cord-id: fz8s6wtq Document date: 2021_4_20
ID: fz8s6wtq
Snippet: Respiratory syncytial virus (RSV) bronchiolitis is a leading cause of infant hospitalization and mortality. We previously identified that prostaglandin D2 (PGD2), released following RSV infection of primary human airway epithelial cells or pneumonia virus of mice (PVM) infection of neonatal mice, elicits pro- or antiviral innate immune responses as a consequence of D-type prostanoid receptor 2 (DP2) or DP1 activation, respectively. Here, we sought to determine whether treatment with the DP1 agon
Document: Respiratory syncytial virus (RSV) bronchiolitis is a leading cause of infant hospitalization and mortality. We previously identified that prostaglandin D2 (PGD2), released following RSV infection of primary human airway epithelial cells or pneumonia virus of mice (PVM) infection of neonatal mice, elicits pro- or antiviral innate immune responses as a consequence of D-type prostanoid receptor 2 (DP2) or DP1 activation, respectively. Here, we sought to determine whether treatment with the DP1 agonist BW245c decreases the severity of bronchiolitis in PVM-infected neonatal mice. Consistent with previous findings, BW245c treatment increased IFN-λ production and decreased viral load in week 1 of the infection. However, unexpectedly, BW245c treatment increased mortality in week 2 of the infection. This increased morbidity was associated with viral spread to the parenchyma, an increased cellular infiltrate of TNF-α-producing cells (neutrophils, monocytes, and CD4(+) T cells), and the heightened production of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. These phenotypes, as well as the increased mortality, were significantly attenuated following the administration of anti-TNF-α to PVM-infected, BW245c-treated mice. In summary, pharmacological activation of the DP1 receptor in PVM-infected neonatal mice boosts antiviral innate and adaptive immunity, however, this is ultimately detrimental, as a consequence of increased TNF-α-induced morbidity and mortality.
Search related documents:
Co phrase search for related documents- acid metabolism and lung function: 1, 2, 3
- acid metabolism and lung inflammation: 1, 2, 3
- acid metabolism and lung injury: 1
- acid metabolism and lung pathology: 1
- acid metabolism and lung tissue: 1
- activate neutrophil and adaptive immune response: 1
- activate neutrophil and lung function: 1
- activate neutrophil and lung injury: 1
- activate neutrophil and lung neutrophil: 1
- activate neutrophil and lung tissue: 1
Co phrase search for related documents, hyperlinks ordered by date