PMC:3291650 / 17624-25395 JSON TXT

Annnotations TAB JSON ListView MergeView

test3

2_test

{"project":"2_test","denotations":[{"id":"22396652-17277103-98461858","span":{"begin":3017,"end":3019},"obj":"17277103"},{"id":"22396652-6206190-98461859","span":{"begin":3898,"end":3900},"obj":"6206190"},{"id":"22396652-1552285-98461860","span":{"begin":3904,"end":3906},"obj":"1552285"},{"id":"22396652-17579060-98461861","span":{"begin":3910,"end":3912},"obj":"17579060"},{"id":"22396652-17213831-98461862","span":{"begin":6409,"end":6411},"obj":"17213831"}],"text":"A20 deficiency in myeloid cells protects against IAV lung infection\nTo determine the role of A20 expression in myeloid cells during an IAV infection in vivo, we intranasally inoculated both A20myel-KO mice and control littermates with a sublethal dose of the mouse adapted IAV X-47 (H3N2) strain and monitored morbidity in terms of weight loss. A20myel-KO mice showed reduced weight loss compared to wild type control littermates and recovered faster from the viral challenge (figure 3A). Also, total protein concentration in BAL fluid, which reflects lung damage and vascular leakage, was increased significantly at 7 and 10 days post infection in both wild type and A20myel-KO mice, and was slightly lower in A20myel-KO mice (data not shown). Next, we measured pulmonary viral titers at 4, 7 and 10 days post infection. No differences in viral titers were observed in A20myel-KO mice versus wild type mice at day 4 and 7 post infection. However, after 10 days, almost no virus could be detected in the lungs of A20myel-KO mice while abundant infectious viral particles could still be isolated from lungs of all wild type mice (figure 3B). This indicates that loss of A20 in myeloid cells does not affect early viral replication but contributes to viral clearance at later stages during infection.\n10.1371/journal.ppat.1002570.g003 Figure 3 A20 deficiency in myeloid cells protects against IAV lung infection.\nA20myel-WT and A20myel-KO mice were infected intranasally with a sublethal dose of IAV and weight loss was monitored (A). At day 4, 7 and 10 post infection (p.i.) viral titers in the lung were measured and expressed as mean TCID50 (B). The dashed line represents the detection limit. ND, not detectable. BAL was isolated from IAV infected mice at 4, 7 and 10 days p.i. and KC, MIP-2, MCP-1, IL-6 and IFNα protein levels were analyzed by ELISA and multiplexing technologies (C). Absolute numbers of resident alveolar macrophages, neutrophils and monocytes in BAL were analyzed by flow cytometry at 4, 7 and 10 days p.i. (D). Numbers are averages +/− SEM of at least 5 mice per group and are representative of 2 independent experiments. *p\u003c0.05; **p\u003c0.01. To verify if A20 deficiency in myeloid cells affects IAV-induced gene expression in the lung, we analyzed the levels of several chemokines and cytokines in the bronchoalveolar lavage (BAL) at day 4, 7 and day 10 following infection. Levels of KC and MIP-2 chemokines, as well as IL-6 were significantly higher at day 7 p.i. in BAL from IAV infected A20myel-KO mice compared to IAV infected wild type mice (figure 3C). Unlike our observations with in vitro stimulated primary macrophages we could not detect a significant increase in MCP-1 or IFNα production in the lungs of A20myel-KO animals (figure 3C). KC is the murine orthologue of IL-8 and serves together with MIP-2 as a chemoattractant for neutrophils, while MCP-1 is mainly known as a chemoattractant for monocytes, which eventually develop into macrophages upon entering the alveolar lumen [60]. Consistent with the higher KC and MIP-2 levels in A20myel-KO mice, the number of neutrophils (CD11b+ Ly6C+ Ly6G+ F4/80−) that were recruited in the bronchoalveolar spaces upon IAV infection was clearly higher throughout infection in A20myel-KO mice compared to control animals (figure 3D). Although we could detect a significant increase in monocyte (CD11b+ Ly6C+) recruitment at day 4 post infection, this was not evident at later time points after infection (figure 3D), which is consistent with the equal expression of MCP-1 in both groups of mice. The number of resident alveolar macrophages (autofluorescent+ CD11c+ F4/80+ CD11b−) was also elevated in A20myel-KO mice but did not differ significantly between IAV infected or mock infected mice (figure 3D). Elimination of IAV infected cells depends on the clonal expansion of virus specific cytotoxic CD8+ T cells (CTL) [61], [62], [63]. To test whether A20 expression in myeloid cells regulates the antiviral CTL response, total CD8+ T cells and virus specific Granzyme B (GrB) and IFNγ expressing CD8+ T cells were measured in BAL and lung parenchyma of wild type and A20myel-KO mice. A clear increase in CD8+ T cells could be detected at day 7 and 10 post infection, but no differences were observed between A20myel-KO and wild type mice (figure S2A and figure S2C). Also, the number of GrB and IFNγ CD8+ T cells as well as IFNγ expression levels in the lungs were not altered by the absence of A20 in myeloid cells (figure S2A–C).\nProtection against IAV infection is also provided by the humoral immune response. To test whether loss of A20 in myeloid cells affects B cell mediated immunity, we determined hemagglutinin (HA) antibody titers in the serum of A20myel-KO and wild type littermates. However, no differences could be detected between wild type and A20myel-KO animals (figure S2D), indicating that humoral immunity is not affected by A20 expression in myeloid cells. Together, these data suggest that mechanisms other than adaptive immunity, such as an increased innate immune response, characterized by an increased influx of neutrophils and increased numbers of alveolar macrophages, contribute to the better viral clearance in A20myel-KO mice.\nIt is generally believed that IAV-induced mortality is due to an excessive proinflammatory response in the lung. We therefore analyzed whether the increased proinflammatory cytokine production and infiltration of proinflammatory cells in A20myel-KO mice affects mortality induced by intranasal infection with a lethal dose of IAV X-47. Surprisingly, almost all A20myel-KO mice survived (10/11), while all control mice succumbed (0/11) within 16 days after infection (figure 4A). A20myel-KO mice still showed significant weight loss and lung damage (as reflected by increased total protein concentration in the BAL; data not shown) during the course of infection but were able to recover, in contrast to wild type mice that succumbed (figure 4B). Similar to our observations with sublethal IAV infection, pulmonary KC and MIP-2 production was stronger in A20myel-KO animals compared to wild type mice following lethal IAV infection (figure 4C), which correlates with the increased numbers of neutrophils in the lungs of these mice (figure 4C). Also levels of the proinflammatory cytokines IL-6, TNF and IL-1β, which are often associated with immunopathogenesis in humans [64], were increased in the lungs of A20myel-KO mice compared to control animals (figure 4C and figure S3A). Again, MCP-1 production was not increased and even lower in A20myel-KO mice (figure 4C), and also monocyte recruitment was not different between both groups of mice. We could also not detect any differences in viral clearance or antiviral adaptive immunity at 6 h post infection (figure S3B–F). Collectively these data indicate that A20 deficiency in myeloid cells is associated with an increased innate immune response and protection against a lethal IAV infection.\n10.1371/journal.ppat.1002570.g004 Figure 4 A20 deficiency in myeloid cells protects against lethal IAV infection.\nA20myel-WT (n = 11) and A20myel-KO (n = 11) mice were intranasally infected with a lethal dose of IAV and survival (p\u003c0.001) (A) and weight loss +/− SEM (B) was monitored for respectively 21 and 15 days p.i. BAL fluid was collected from wild type (A20myel-WT) and A20myel-KO mice 6 days following infection with a lethal dose IAV and KC, MIP-2, MCP-1, IL-6 and IFNα protein levels were determined (C). Absolute numbers of alveolar macrophages, neutrophils and monocytes in BAL were analyzed by flow cytometry at 6 days p.i. (D). Numbers are averages +/− SEM of at least 5 mice per group. Data are representative of 2 independent experiments. *p\u003c0.05; **p\u003c0.01, ***p\u003c0.001."}

pmc-enju-pas

bionlp-st-ge-2016-test-proteins

bionlp-st-ge-2016-uniprot

UBERON-AE

{"project":"UBERON-AE","denotations":[{"id":"T20778","span":{"begin":1595,"end":1599},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T20777","span":{"begin":1396,"end":1400},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T8719","span":{"begin":4729,"end":4734},"obj":"http://purl.obolibrary.org/obo/UBERON_0001977"},{"id":"T8718","span":{"begin":4119,"end":4129},"obj":"http://purl.obolibrary.org/obo/UBERON_0000353"},{"id":"T8717","span":{"begin":4114,"end":4129},"obj":"http://purl.obolibrary.org/obo/UBERON_0008946"},{"id":"T8716","span":{"begin":6436,"end":6441},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T8715","span":{"begin":6248,"end":6253},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T8714","span":{"begin":5774,"end":5778},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T8713","span":{"begin":5345,"end":5349},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T8712","span":{"begin":4114,"end":4118},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T8711","span":{"begin":2254,"end":2258},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T8710","span":{"begin":552,"end":556},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T8709","span":{"begin":53,"end":57},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"A20 deficiency in myeloid cells protects against IAV lung infection\nTo determine the role of A20 expression in myeloid cells during an IAV infection in vivo, we intranasally inoculated both A20myel-KO mice and control littermates with a sublethal dose of the mouse adapted IAV X-47 (H3N2) strain and monitored morbidity in terms of weight loss. A20myel-KO mice showed reduced weight loss compared to wild type control littermates and recovered faster from the viral challenge (figure 3A). Also, total protein concentration in BAL fluid, which reflects lung damage and vascular leakage, was increased significantly at 7 and 10 days post infection in both wild type and A20myel-KO mice, and was slightly lower in A20myel-KO mice (data not shown). Next, we measured pulmonary viral titers at 4, 7 and 10 days post infection. No differences in viral titers were observed in A20myel-KO mice versus wild type mice at day 4 and 7 post infection. However, after 10 days, almost no virus could be detected in the lungs of A20myel-KO mice while abundant infectious viral particles could still be isolated from lungs of all wild type mice (figure 3B). This indicates that loss of A20 in myeloid cells does not affect early viral replication but contributes to viral clearance at later stages during infection.\n10.1371/journal.ppat.1002570.g003 Figure 3 A20 deficiency in myeloid cells protects against IAV lung infection.\nA20myel-WT and A20myel-KO mice were infected intranasally with a sublethal dose of IAV and weight loss was monitored (A). At day 4, 7 and 10 post infection (p.i.) viral titers in the lung were measured and expressed as mean TCID50 (B). The dashed line represents the detection limit. ND, not detectable. BAL was isolated from IAV infected mice at 4, 7 and 10 days p.i. and KC, MIP-2, MCP-1, IL-6 and IFNα protein levels were analyzed by ELISA and multiplexing technologies (C). Absolute numbers of resident alveolar macrophages, neutrophils and monocytes in BAL were analyzed by flow cytometry at 4, 7 and 10 days p.i. (D). Numbers are averages +/− SEM of at least 5 mice per group and are representative of 2 independent experiments. *p\u003c0.05; **p\u003c0.01. To verify if A20 deficiency in myeloid cells affects IAV-induced gene expression in the lung, we analyzed the levels of several chemokines and cytokines in the bronchoalveolar lavage (BAL) at day 4, 7 and day 10 following infection. Levels of KC and MIP-2 chemokines, as well as IL-6 were significantly higher at day 7 p.i. in BAL from IAV infected A20myel-KO mice compared to IAV infected wild type mice (figure 3C). Unlike our observations with in vitro stimulated primary macrophages we could not detect a significant increase in MCP-1 or IFNα production in the lungs of A20myel-KO animals (figure 3C). KC is the murine orthologue of IL-8 and serves together with MIP-2 as a chemoattractant for neutrophils, while MCP-1 is mainly known as a chemoattractant for monocytes, which eventually develop into macrophages upon entering the alveolar lumen [60]. Consistent with the higher KC and MIP-2 levels in A20myel-KO mice, the number of neutrophils (CD11b+ Ly6C+ Ly6G+ F4/80−) that were recruited in the bronchoalveolar spaces upon IAV infection was clearly higher throughout infection in A20myel-KO mice compared to control animals (figure 3D). Although we could detect a significant increase in monocyte (CD11b+ Ly6C+) recruitment at day 4 post infection, this was not evident at later time points after infection (figure 3D), which is consistent with the equal expression of MCP-1 in both groups of mice. The number of resident alveolar macrophages (autofluorescent+ CD11c+ F4/80+ CD11b−) was also elevated in A20myel-KO mice but did not differ significantly between IAV infected or mock infected mice (figure 3D). Elimination of IAV infected cells depends on the clonal expansion of virus specific cytotoxic CD8+ T cells (CTL) [61], [62], [63]. To test whether A20 expression in myeloid cells regulates the antiviral CTL response, total CD8+ T cells and virus specific Granzyme B (GrB) and IFNγ expressing CD8+ T cells were measured in BAL and lung parenchyma of wild type and A20myel-KO mice. A clear increase in CD8+ T cells could be detected at day 7 and 10 post infection, but no differences were observed between A20myel-KO and wild type mice (figure S2A and figure S2C). Also, the number of GrB and IFNγ CD8+ T cells as well as IFNγ expression levels in the lungs were not altered by the absence of A20 in myeloid cells (figure S2A–C).\nProtection against IAV infection is also provided by the humoral immune response. To test whether loss of A20 in myeloid cells affects B cell mediated immunity, we determined hemagglutinin (HA) antibody titers in the serum of A20myel-KO and wild type littermates. However, no differences could be detected between wild type and A20myel-KO animals (figure S2D), indicating that humoral immunity is not affected by A20 expression in myeloid cells. Together, these data suggest that mechanisms other than adaptive immunity, such as an increased innate immune response, characterized by an increased influx of neutrophils and increased numbers of alveolar macrophages, contribute to the better viral clearance in A20myel-KO mice.\nIt is generally believed that IAV-induced mortality is due to an excessive proinflammatory response in the lung. We therefore analyzed whether the increased proinflammatory cytokine production and infiltration of proinflammatory cells in A20myel-KO mice affects mortality induced by intranasal infection with a lethal dose of IAV X-47. Surprisingly, almost all A20myel-KO mice survived (10/11), while all control mice succumbed (0/11) within 16 days after infection (figure 4A). A20myel-KO mice still showed significant weight loss and lung damage (as reflected by increased total protein concentration in the BAL; data not shown) during the course of infection but were able to recover, in contrast to wild type mice that succumbed (figure 4B). Similar to our observations with sublethal IAV infection, pulmonary KC and MIP-2 production was stronger in A20myel-KO animals compared to wild type mice following lethal IAV infection (figure 4C), which correlates with the increased numbers of neutrophils in the lungs of these mice (figure 4C). Also levels of the proinflammatory cytokines IL-6, TNF and IL-1β, which are often associated with immunopathogenesis in humans [64], were increased in the lungs of A20myel-KO mice compared to control animals (figure 4C and figure S3A). Again, MCP-1 production was not increased and even lower in A20myel-KO mice (figure 4C), and also monocyte recruitment was not different between both groups of mice. We could also not detect any differences in viral clearance or antiviral adaptive immunity at 6 h post infection (figure S3B–F). Collectively these data indicate that A20 deficiency in myeloid cells is associated with an increased innate immune response and protection against a lethal IAV infection.\n10.1371/journal.ppat.1002570.g004 Figure 4 A20 deficiency in myeloid cells protects against lethal IAV infection.\nA20myel-WT (n = 11) and A20myel-KO (n = 11) mice were intranasally infected with a lethal dose of IAV and survival (p\u003c0.001) (A) and weight loss +/− SEM (B) was monitored for respectively 21 and 15 days p.i. BAL fluid was collected from wild type (A20myel-WT) and A20myel-KO mice 6 days following infection with a lethal dose IAV and KC, MIP-2, MCP-1, IL-6 and IFNα protein levels were determined (C). Absolute numbers of alveolar macrophages, neutrophils and monocytes in BAL were analyzed by flow cytometry at 6 days p.i. (D). Numbers are averages +/− SEM of at least 5 mice per group. Data are representative of 2 independent experiments. *p\u003c0.05; **p\u003c0.01, ***p\u003c0.001."}

GO-BP

GO-MF

{"project":"GO-MF","denotations":[{"id":"T21239","span":{"begin":7451,"end":7455},"obj":"http://purl.obolibrary.org/obo/GO_0005138"},{"id":"T21238","span":{"begin":7448,"end":7453},"obj":"http://purl.obolibrary.org/obo/GO_0005149"},{"id":"T20798","span":{"begin":1800,"end":1805},"obj":"http://purl.obolibrary.org/obo/GO_0005149"},{"id":"T20797","span":{"begin":1796,"end":1799},"obj":"http://purl.obolibrary.org/obo/GO_0004298"},{"id":"T20799","span":{"begin":1803,"end":1807},"obj":"http://purl.obolibrary.org/obo/GO_0005138"},{"id":"T21237","span":{"begin":7444,"end":7447},"obj":"http://purl.obolibrary.org/obo/GO_0004298"},{"id":"T8862","span":{"begin":4706,"end":4714},"obj":"http://purl.obolibrary.org/obo/GO_0003823"},{"id":"T8861","span":{"begin":2803,"end":2807},"obj":"http://purl.obolibrary.org/obo/GO_0005153"},{"id":"T8860","span":{"begin":6524,"end":6527},"obj":"http://purl.obolibrary.org/obo/GO_0004298"},{"id":"T8859","span":{"begin":3544,"end":3547},"obj":"http://purl.obolibrary.org/obo/GO_0004298"},{"id":"T8858","span":{"begin":2883,"end":2886},"obj":"http://purl.obolibrary.org/obo/GO_0004298"},{"id":"T8857","span":{"begin":2699,"end":2702},"obj":"http://purl.obolibrary.org/obo/GO_0004298"},{"id":"T8856","span":{"begin":6326,"end":6330},"obj":"http://purl.obolibrary.org/obo/GO_0005138"},{"id":"T8855","span":{"begin":2445,"end":2449},"obj":"http://purl.obolibrary.org/obo/GO_0005138"}],"text":"A20 deficiency in myeloid cells protects against IAV lung infection\nTo determine the role of A20 expression in myeloid cells during an IAV infection in vivo, we intranasally inoculated both A20myel-KO mice and control littermates with a sublethal dose of the mouse adapted IAV X-47 (H3N2) strain and monitored morbidity in terms of weight loss. A20myel-KO mice showed reduced weight loss compared to wild type control littermates and recovered faster from the viral challenge (figure 3A). Also, total protein concentration in BAL fluid, which reflects lung damage and vascular leakage, was increased significantly at 7 and 10 days post infection in both wild type and A20myel-KO mice, and was slightly lower in A20myel-KO mice (data not shown). Next, we measured pulmonary viral titers at 4, 7 and 10 days post infection. No differences in viral titers were observed in A20myel-KO mice versus wild type mice at day 4 and 7 post infection. However, after 10 days, almost no virus could be detected in the lungs of A20myel-KO mice while abundant infectious viral particles could still be isolated from lungs of all wild type mice (figure 3B). This indicates that loss of A20 in myeloid cells does not affect early viral replication but contributes to viral clearance at later stages during infection.\n10.1371/journal.ppat.1002570.g003 Figure 3 A20 deficiency in myeloid cells protects against IAV lung infection.\nA20myel-WT and A20myel-KO mice were infected intranasally with a sublethal dose of IAV and weight loss was monitored (A). At day 4, 7 and 10 post infection (p.i.) viral titers in the lung were measured and expressed as mean TCID50 (B). The dashed line represents the detection limit. ND, not detectable. BAL was isolated from IAV infected mice at 4, 7 and 10 days p.i. and KC, MIP-2, MCP-1, IL-6 and IFNα protein levels were analyzed by ELISA and multiplexing technologies (C). Absolute numbers of resident alveolar macrophages, neutrophils and monocytes in BAL were analyzed by flow cytometry at 4, 7 and 10 days p.i. (D). Numbers are averages +/− SEM of at least 5 mice per group and are representative of 2 independent experiments. *p\u003c0.05; **p\u003c0.01. To verify if A20 deficiency in myeloid cells affects IAV-induced gene expression in the lung, we analyzed the levels of several chemokines and cytokines in the bronchoalveolar lavage (BAL) at day 4, 7 and day 10 following infection. Levels of KC and MIP-2 chemokines, as well as IL-6 were significantly higher at day 7 p.i. in BAL from IAV infected A20myel-KO mice compared to IAV infected wild type mice (figure 3C). Unlike our observations with in vitro stimulated primary macrophages we could not detect a significant increase in MCP-1 or IFNα production in the lungs of A20myel-KO animals (figure 3C). KC is the murine orthologue of IL-8 and serves together with MIP-2 as a chemoattractant for neutrophils, while MCP-1 is mainly known as a chemoattractant for monocytes, which eventually develop into macrophages upon entering the alveolar lumen [60]. Consistent with the higher KC and MIP-2 levels in A20myel-KO mice, the number of neutrophils (CD11b+ Ly6C+ Ly6G+ F4/80−) that were recruited in the bronchoalveolar spaces upon IAV infection was clearly higher throughout infection in A20myel-KO mice compared to control animals (figure 3D). Although we could detect a significant increase in monocyte (CD11b+ Ly6C+) recruitment at day 4 post infection, this was not evident at later time points after infection (figure 3D), which is consistent with the equal expression of MCP-1 in both groups of mice. The number of resident alveolar macrophages (autofluorescent+ CD11c+ F4/80+ CD11b−) was also elevated in A20myel-KO mice but did not differ significantly between IAV infected or mock infected mice (figure 3D). Elimination of IAV infected cells depends on the clonal expansion of virus specific cytotoxic CD8+ T cells (CTL) [61], [62], [63]. To test whether A20 expression in myeloid cells regulates the antiviral CTL response, total CD8+ T cells and virus specific Granzyme B (GrB) and IFNγ expressing CD8+ T cells were measured in BAL and lung parenchyma of wild type and A20myel-KO mice. A clear increase in CD8+ T cells could be detected at day 7 and 10 post infection, but no differences were observed between A20myel-KO and wild type mice (figure S2A and figure S2C). Also, the number of GrB and IFNγ CD8+ T cells as well as IFNγ expression levels in the lungs were not altered by the absence of A20 in myeloid cells (figure S2A–C).\nProtection against IAV infection is also provided by the humoral immune response. To test whether loss of A20 in myeloid cells affects B cell mediated immunity, we determined hemagglutinin (HA) antibody titers in the serum of A20myel-KO and wild type littermates. However, no differences could be detected between wild type and A20myel-KO animals (figure S2D), indicating that humoral immunity is not affected by A20 expression in myeloid cells. Together, these data suggest that mechanisms other than adaptive immunity, such as an increased innate immune response, characterized by an increased influx of neutrophils and increased numbers of alveolar macrophages, contribute to the better viral clearance in A20myel-KO mice.\nIt is generally believed that IAV-induced mortality is due to an excessive proinflammatory response in the lung. We therefore analyzed whether the increased proinflammatory cytokine production and infiltration of proinflammatory cells in A20myel-KO mice affects mortality induced by intranasal infection with a lethal dose of IAV X-47. Surprisingly, almost all A20myel-KO mice survived (10/11), while all control mice succumbed (0/11) within 16 days after infection (figure 4A). A20myel-KO mice still showed significant weight loss and lung damage (as reflected by increased total protein concentration in the BAL; data not shown) during the course of infection but were able to recover, in contrast to wild type mice that succumbed (figure 4B). Similar to our observations with sublethal IAV infection, pulmonary KC and MIP-2 production was stronger in A20myel-KO animals compared to wild type mice following lethal IAV infection (figure 4C), which correlates with the increased numbers of neutrophils in the lungs of these mice (figure 4C). Also levels of the proinflammatory cytokines IL-6, TNF and IL-1β, which are often associated with immunopathogenesis in humans [64], were increased in the lungs of A20myel-KO mice compared to control animals (figure 4C and figure S3A). Again, MCP-1 production was not increased and even lower in A20myel-KO mice (figure 4C), and also monocyte recruitment was not different between both groups of mice. We could also not detect any differences in viral clearance or antiviral adaptive immunity at 6 h post infection (figure S3B–F). Collectively these data indicate that A20 deficiency in myeloid cells is associated with an increased innate immune response and protection against a lethal IAV infection.\n10.1371/journal.ppat.1002570.g004 Figure 4 A20 deficiency in myeloid cells protects against lethal IAV infection.\nA20myel-WT (n = 11) and A20myel-KO (n = 11) mice were intranasally infected with a lethal dose of IAV and survival (p\u003c0.001) (A) and weight loss +/− SEM (B) was monitored for respectively 21 and 15 days p.i. BAL fluid was collected from wild type (A20myel-WT) and A20myel-KO mice 6 days following infection with a lethal dose IAV and KC, MIP-2, MCP-1, IL-6 and IFNα protein levels were determined (C). Absolute numbers of alveolar macrophages, neutrophils and monocytes in BAL were analyzed by flow cytometry at 6 days p.i. (D). Numbers are averages +/− SEM of at least 5 mice per group. Data are representative of 2 independent experiments. *p\u003c0.05; **p\u003c0.01, ***p\u003c0.001."}

GO-CC

sentences

simple1

BioNLP16_DUT

BioNLP16_Messiy

DLUT931

bionlp-st-ge-2016-test-ihmc

bionlp-st-ge-2016-spacy-parsed

bionlp-st-ge-2016-test-tees

testone

PMC:3291650 / 17624-25395 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:3291650 / 17624-25395 JSON TXT