Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-107 |
Sentence |
denotes |
Role of type I interferon signaling in human metapneumovirus pathogenesis and control of viral replication. |
T2 |
108-119 |
Sentence |
denotes |
UNLABELLED: |
T3 |
120-309 |
Sentence |
denotes |
Type I IFN signaling, which is initiated through activation of the alpha interferon receptor (IFNAR), regulates the expression of proteins that are crucial contributors to immune responses. |
T4 |
310-551 |
Sentence |
denotes |
Paramyxoviruses, including human metapneumovirus (HMPV), have evolved mechanisms to inhibit IFNAR signaling, but the specific contribution of IFNAR signaling to the control of HMPV replication, pathogenesis, and adaptive immunity is unknown. |
T5 |
552-685 |
Sentence |
denotes |
We used IFNAR-deficient (IFNAR(-/-)) mice to assess the effect of IFNAR signaling on HMPV replication and the CD8(+) T cell response. |
T6 |
686-837 |
Sentence |
denotes |
HMPV-infected IFNAR(-/-) mice had a higher peak of early viral replication but cleared the virus with kinetics similar to those of wild-type (WT) mice. |
T7 |
838-938 |
Sentence |
denotes |
However, IFNAR(-/-) mice infected with HMPV displayed less airway dysfunction and lung inflammation. |
T8 |
939-1092 |
Sentence |
denotes |
CD8(+) T cells of IFNAR(-/-) mice after HMPV infection expressed levels of the inhibitory receptor programmed death 1 (PD-1) similar to those of WT mice. |
T9 |
1093-1324 |
Sentence |
denotes |
However, despite lower expression of inhibitory programmed death ligand 1 (PD-L1), HMPV-specific CD8(+) T cells of IFNAR(-/-) mice were more functionally impaired than those of WT mice and upregulated the inhibitory receptor Tim-3. |
T10 |
1325-1526 |
Sentence |
denotes |
Analysis of the antigen-presenting cell subsets in the lungs revealed that the expansion of PD-L1(low) dendritic cells (DCs), but not PD-L1(high) alveolar macrophages, was dependent on IFNAR signaling. |
T11 |
1527-1711 |
Sentence |
denotes |
Collectively, our results indicate a role for IFNAR signaling in the early control of HMPV replication, disease progression, and the development of an optimal adaptive immune response. |
T12 |
1712-1807 |
Sentence |
denotes |
Moreover, our findings suggest an IFNAR-independent mechanism of lung CD8(+) T cell impairment. |
T13 |
1808-1819 |
Sentence |
denotes |
IMPORTANCE: |
T14 |
1820-1897 |
Sentence |
denotes |
Human metapneumovirus (HMPV) is a leading cause of acute respiratory illness. |
T15 |
1898-2079 |
Sentence |
denotes |
CD8(+) T cells are critical for clearing viral infection, yet recent evidence shows that HMPV and other respiratory viruses induce CD8(+) T cell impairment via PD-1-PD-L1 signaling. |
T16 |
2080-2237 |
Sentence |
denotes |
We sought to understand the role of type I interferon (IFN) in the innate and adaptive immune responses to HMPV by using a mouse model lacking IFN signaling. |
T17 |
2238-2456 |
Sentence |
denotes |
Although HMPV titers were higher in the absence of type I IFN, virus was nonetheless cleared and mice were less ill, indicating that type I IFN is not required to resolve HMPV infection but contributes to pathogenesis. |
T18 |
2457-2610 |
Sentence |
denotes |
Further, despite lower levels of the inhibitory ligand PD-L1 in mice lacking type I IFN, CD8(+) T cells were more impaired in these mice than in WT mice. |
T19 |
2611-2751 |
Sentence |
denotes |
Our data suggest that specific antigen-presenting cell subsets and the inhibitory receptor Tim-3 may contribute to CD8(+) T cell impairment. |
T1 |
0-107 |
Sentence |
denotes |
Role of type I interferon signaling in human metapneumovirus pathogenesis and control of viral replication. |
T2 |
108-119 |
Sentence |
denotes |
UNLABELLED: |
T3 |
120-309 |
Sentence |
denotes |
Type I IFN signaling, which is initiated through activation of the alpha interferon receptor (IFNAR), regulates the expression of proteins that are crucial contributors to immune responses. |
T4 |
310-551 |
Sentence |
denotes |
Paramyxoviruses, including human metapneumovirus (HMPV), have evolved mechanisms to inhibit IFNAR signaling, but the specific contribution of IFNAR signaling to the control of HMPV replication, pathogenesis, and adaptive immunity is unknown. |
T5 |
552-685 |
Sentence |
denotes |
We used IFNAR-deficient (IFNAR(-/-)) mice to assess the effect of IFNAR signaling on HMPV replication and the CD8(+) T cell response. |
T6 |
686-837 |
Sentence |
denotes |
HMPV-infected IFNAR(-/-) mice had a higher peak of early viral replication but cleared the virus with kinetics similar to those of wild-type (WT) mice. |
T7 |
838-938 |
Sentence |
denotes |
However, IFNAR(-/-) mice infected with HMPV displayed less airway dysfunction and lung inflammation. |
T8 |
939-1092 |
Sentence |
denotes |
CD8(+) T cells of IFNAR(-/-) mice after HMPV infection expressed levels of the inhibitory receptor programmed death 1 (PD-1) similar to those of WT mice. |
T9 |
1093-1324 |
Sentence |
denotes |
However, despite lower expression of inhibitory programmed death ligand 1 (PD-L1), HMPV-specific CD8(+) T cells of IFNAR(-/-) mice were more functionally impaired than those of WT mice and upregulated the inhibitory receptor Tim-3. |
T10 |
1325-1526 |
Sentence |
denotes |
Analysis of the antigen-presenting cell subsets in the lungs revealed that the expansion of PD-L1(low) dendritic cells (DCs), but not PD-L1(high) alveolar macrophages, was dependent on IFNAR signaling. |
T11 |
1527-1711 |
Sentence |
denotes |
Collectively, our results indicate a role for IFNAR signaling in the early control of HMPV replication, disease progression, and the development of an optimal adaptive immune response. |
T12 |
1712-1807 |
Sentence |
denotes |
Moreover, our findings suggest an IFNAR-independent mechanism of lung CD8(+) T cell impairment. |
T13 |
1808-1819 |
Sentence |
denotes |
IMPORTANCE: |
T14 |
1820-1897 |
Sentence |
denotes |
Human metapneumovirus (HMPV) is a leading cause of acute respiratory illness. |
T15 |
1898-2079 |
Sentence |
denotes |
CD8(+) T cells are critical for clearing viral infection, yet recent evidence shows that HMPV and other respiratory viruses induce CD8(+) T cell impairment via PD-1-PD-L1 signaling. |
T16 |
2080-2237 |
Sentence |
denotes |
We sought to understand the role of type I interferon (IFN) in the innate and adaptive immune responses to HMPV by using a mouse model lacking IFN signaling. |
T17 |
2238-2456 |
Sentence |
denotes |
Although HMPV titers were higher in the absence of type I IFN, virus was nonetheless cleared and mice were less ill, indicating that type I IFN is not required to resolve HMPV infection but contributes to pathogenesis. |
T18 |
2457-2610 |
Sentence |
denotes |
Further, despite lower levels of the inhibitory ligand PD-L1 in mice lacking type I IFN, CD8(+) T cells were more impaired in these mice than in WT mice. |
T19 |
2611-2751 |
Sentence |
denotes |
Our data suggest that specific antigen-presenting cell subsets and the inhibitory receptor Tim-3 may contribute to CD8(+) T cell impairment. |