Type 1 IFN Induction by Cytosolic Nucleic Acid Is Intact in Neonatal Mononuclear Cells, Contrasting Starkly with Neonatal Hyporesponsiveness to TLR Ligation Due to Independence from Endosome-Mediated IRF3 Activation [CLINICAL AND HUMAN IMMUNOLOGY]

Publication Date:
2018-08-07
Publisher:
The American Association of Immunologists (AAI)
Print ISSN:
0022-1767
Electronic ISSN:
1550-6606
Topics:
Medicine
Published by:
http://www.aai.org/
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autor Brennan, K., OLeary, B. D., Mc Laughlin, D., Breen, E. P., Connolly, E., Ali, N., ODriscoll, D. N., Ozaki, E., Mahony, R., Mulfaul, K., Ryan, A. M., Ni Chianain, A., McHugh, A., Molloy, E. J., Hogan, A. E., Paran, S., McAuliffe, F. M., Doyle, S. L.
beschreibung Two million infants die each year from infectious diseases before they reach 12 mo; many of these diseases are vaccine preventable in older populations. Pattern recognition receptors represent the critical front-line defense against pathogens. Evidence suggests that the innate immune system does not fully develop until puberty, contributing to impaired response to infection and impaired vaccine responses in neonates, infants, and children. The activity of the pattern recognition receptor family of cytosolic nucleic acid (CNA) sensors in this pediatric population has not been reported. We show that in direct contrast to weak TLR-induced type I IFN in human cord blood mononuclear cells, cord blood mononuclear cells are capable of initiating a potent response to CNA, inducing both antiviral type I IFN and, unexpectedly, proinflammatory TNF-α. A deficiency in Rab11-GTPase endosome formation and consequent lack of IRF3 activation in neonatal monocytes is at least in part responsible for the marked disparity in TLR-induced IFN production between neonatal and adult monocytes. CNA receptors do not rely on endosome formation, and therefore, these responses remain intact in neonates. Heightened neonatal responses to CNA challenge are maintained in children up to 2 y of age and, in marked contrast to TLR4/9 agonists, result in IL-12p70 and IFN- generation. CNA sensors induce robust antiviral and proinflammatory pathways in neonates and children and possess great potential for use as immunostimulants or vaccine adjuvants for targeted neonatal and pediatric populations to promote cell-mediated immunity against invasive infectious disease.
citation_standardnr 6315483
datenlieferant ipn_articles
feed_id 333
feed_publisher The American Association of Immunologists (AAI)
feed_publisher_url http://www.aai.org/
insertion_date 2018-08-07
journaleissn 1550-6606
journalissn 0022-1767
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association of Immunologists (AAI)
quelle Journal of Immunology
relation http://www.jimmunol.org/cgi/content/short/201/4/1131?rss=1
search_space articles
shingle_author_1 Brennan, K., OLeary, B. D., Mc Laughlin, D., Breen, E. P., Connolly, E., Ali, N., ODriscoll, D. N., Ozaki, E., Mahony, R., Mulfaul, K., Ryan, A. M., Ni Chianain, A., McHugh, A., Molloy, E. J., Hogan, A. E., Paran, S., McAuliffe, F. M., Doyle, S. L.
shingle_author_2 Brennan, K., OLeary, B. D., Mc Laughlin, D., Breen, E. P., Connolly, E., Ali, N., ODriscoll, D. N., Ozaki, E., Mahony, R., Mulfaul, K., Ryan, A. M., Ni Chianain, A., McHugh, A., Molloy, E. J., Hogan, A. E., Paran, S., McAuliffe, F. M., Doyle, S. L.
shingle_author_3 Brennan, K., OLeary, B. D., Mc Laughlin, D., Breen, E. P., Connolly, E., Ali, N., ODriscoll, D. N., Ozaki, E., Mahony, R., Mulfaul, K., Ryan, A. M., Ni Chianain, A., McHugh, A., Molloy, E. J., Hogan, A. E., Paran, S., McAuliffe, F. M., Doyle, S. L.
shingle_author_4 Brennan, K., OLeary, B. D., Mc Laughlin, D., Breen, E. P., Connolly, E., Ali, N., ODriscoll, D. N., Ozaki, E., Mahony, R., Mulfaul, K., Ryan, A. M., Ni Chianain, A., McHugh, A., Molloy, E. J., Hogan, A. E., Paran, S., McAuliffe, F. M., Doyle, S. L.
shingle_catch_all_1 Type 1 IFN Induction by Cytosolic Nucleic Acid Is Intact in Neonatal Mononuclear Cells, Contrasting Starkly with Neonatal Hyporesponsiveness to TLR Ligation Due to Independence from Endosome-Mediated IRF3 Activation [CLINICAL AND HUMAN IMMUNOLOGY]
Two million infants die each year from infectious diseases before they reach 12 mo; many of these diseases are vaccine preventable in older populations. Pattern recognition receptors represent the critical front-line defense against pathogens. Evidence suggests that the innate immune system does not fully develop until puberty, contributing to impaired response to infection and impaired vaccine responses in neonates, infants, and children. The activity of the pattern recognition receptor family of cytosolic nucleic acid (CNA) sensors in this pediatric population has not been reported. We show that in direct contrast to weak TLR-induced type I IFN in human cord blood mononuclear cells, cord blood mononuclear cells are capable of initiating a potent response to CNA, inducing both antiviral type I IFN and, unexpectedly, proinflammatory TNF-α. A deficiency in Rab11-GTPase endosome formation and consequent lack of IRF3 activation in neonatal monocytes is at least in part responsible for the marked disparity in TLR-induced IFN production between neonatal and adult monocytes. CNA receptors do not rely on endosome formation, and therefore, these responses remain intact in neonates. Heightened neonatal responses to CNA challenge are maintained in children up to 2 y of age and, in marked contrast to TLR4/9 agonists, result in IL-12p70 and IFN- generation. CNA sensors induce robust antiviral and proinflammatory pathways in neonates and children and possess great potential for use as immunostimulants or vaccine adjuvants for targeted neonatal and pediatric populations to promote cell-mediated immunity against invasive infectious disease.
Brennan, K., OLeary, B. D., Mc Laughlin, D., Breen, E. P., Connolly, E., Ali, N., ODriscoll, D. N., Ozaki, E., Mahony, R., Mulfaul, K., Ryan, A. M., Ni Chianain, A., McHugh, A., Molloy, E. J., Hogan, A. E., Paran, S., McAuliffe, F. M., Doyle, S. L.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_2 Type 1 IFN Induction by Cytosolic Nucleic Acid Is Intact in Neonatal Mononuclear Cells, Contrasting Starkly with Neonatal Hyporesponsiveness to TLR Ligation Due to Independence from Endosome-Mediated IRF3 Activation [CLINICAL AND HUMAN IMMUNOLOGY]
Two million infants die each year from infectious diseases before they reach 12 mo; many of these diseases are vaccine preventable in older populations. Pattern recognition receptors represent the critical front-line defense against pathogens. Evidence suggests that the innate immune system does not fully develop until puberty, contributing to impaired response to infection and impaired vaccine responses in neonates, infants, and children. The activity of the pattern recognition receptor family of cytosolic nucleic acid (CNA) sensors in this pediatric population has not been reported. We show that in direct contrast to weak TLR-induced type I IFN in human cord blood mononuclear cells, cord blood mononuclear cells are capable of initiating a potent response to CNA, inducing both antiviral type I IFN and, unexpectedly, proinflammatory TNF-α. A deficiency in Rab11-GTPase endosome formation and consequent lack of IRF3 activation in neonatal monocytes is at least in part responsible for the marked disparity in TLR-induced IFN production between neonatal and adult monocytes. CNA receptors do not rely on endosome formation, and therefore, these responses remain intact in neonates. Heightened neonatal responses to CNA challenge are maintained in children up to 2 y of age and, in marked contrast to TLR4/9 agonists, result in IL-12p70 and IFN- generation. CNA sensors induce robust antiviral and proinflammatory pathways in neonates and children and possess great potential for use as immunostimulants or vaccine adjuvants for targeted neonatal and pediatric populations to promote cell-mediated immunity against invasive infectious disease.
Brennan, K., OLeary, B. D., Mc Laughlin, D., Breen, E. P., Connolly, E., Ali, N., ODriscoll, D. N., Ozaki, E., Mahony, R., Mulfaul, K., Ryan, A. M., Ni Chianain, A., McHugh, A., Molloy, E. J., Hogan, A. E., Paran, S., McAuliffe, F. M., Doyle, S. L.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_3 Type 1 IFN Induction by Cytosolic Nucleic Acid Is Intact in Neonatal Mononuclear Cells, Contrasting Starkly with Neonatal Hyporesponsiveness to TLR Ligation Due to Independence from Endosome-Mediated IRF3 Activation [CLINICAL AND HUMAN IMMUNOLOGY]
Two million infants die each year from infectious diseases before they reach 12 mo; many of these diseases are vaccine preventable in older populations. Pattern recognition receptors represent the critical front-line defense against pathogens. Evidence suggests that the innate immune system does not fully develop until puberty, contributing to impaired response to infection and impaired vaccine responses in neonates, infants, and children. The activity of the pattern recognition receptor family of cytosolic nucleic acid (CNA) sensors in this pediatric population has not been reported. We show that in direct contrast to weak TLR-induced type I IFN in human cord blood mononuclear cells, cord blood mononuclear cells are capable of initiating a potent response to CNA, inducing both antiviral type I IFN and, unexpectedly, proinflammatory TNF-α. A deficiency in Rab11-GTPase endosome formation and consequent lack of IRF3 activation in neonatal monocytes is at least in part responsible for the marked disparity in TLR-induced IFN production between neonatal and adult monocytes. CNA receptors do not rely on endosome formation, and therefore, these responses remain intact in neonates. Heightened neonatal responses to CNA challenge are maintained in children up to 2 y of age and, in marked contrast to TLR4/9 agonists, result in IL-12p70 and IFN- generation. CNA sensors induce robust antiviral and proinflammatory pathways in neonates and children and possess great potential for use as immunostimulants or vaccine adjuvants for targeted neonatal and pediatric populations to promote cell-mediated immunity against invasive infectious disease.
Brennan, K., OLeary, B. D., Mc Laughlin, D., Breen, E. P., Connolly, E., Ali, N., ODriscoll, D. N., Ozaki, E., Mahony, R., Mulfaul, K., Ryan, A. M., Ni Chianain, A., McHugh, A., Molloy, E. J., Hogan, A. E., Paran, S., McAuliffe, F. M., Doyle, S. L.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_4 Type 1 IFN Induction by Cytosolic Nucleic Acid Is Intact in Neonatal Mononuclear Cells, Contrasting Starkly with Neonatal Hyporesponsiveness to TLR Ligation Due to Independence from Endosome-Mediated IRF3 Activation [CLINICAL AND HUMAN IMMUNOLOGY]
Two million infants die each year from infectious diseases before they reach 12 mo; many of these diseases are vaccine preventable in older populations. Pattern recognition receptors represent the critical front-line defense against pathogens. Evidence suggests that the innate immune system does not fully develop until puberty, contributing to impaired response to infection and impaired vaccine responses in neonates, infants, and children. The activity of the pattern recognition receptor family of cytosolic nucleic acid (CNA) sensors in this pediatric population has not been reported. We show that in direct contrast to weak TLR-induced type I IFN in human cord blood mononuclear cells, cord blood mononuclear cells are capable of initiating a potent response to CNA, inducing both antiviral type I IFN and, unexpectedly, proinflammatory TNF-α. A deficiency in Rab11-GTPase endosome formation and consequent lack of IRF3 activation in neonatal monocytes is at least in part responsible for the marked disparity in TLR-induced IFN production between neonatal and adult monocytes. CNA receptors do not rely on endosome formation, and therefore, these responses remain intact in neonates. Heightened neonatal responses to CNA challenge are maintained in children up to 2 y of age and, in marked contrast to TLR4/9 agonists, result in IL-12p70 and IFN- generation. CNA sensors induce robust antiviral and proinflammatory pathways in neonates and children and possess great potential for use as immunostimulants or vaccine adjuvants for targeted neonatal and pediatric populations to promote cell-mediated immunity against invasive infectious disease.
Brennan, K., OLeary, B. D., Mc Laughlin, D., Breen, E. P., Connolly, E., Ali, N., ODriscoll, D. N., Ozaki, E., Mahony, R., Mulfaul, K., Ryan, A. M., Ni Chianain, A., McHugh, A., Molloy, E. J., Hogan, A. E., Paran, S., McAuliffe, F. M., Doyle, S. L.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_title_1 Type 1 IFN Induction by Cytosolic Nucleic Acid Is Intact in Neonatal Mononuclear Cells, Contrasting Starkly with Neonatal Hyporesponsiveness to TLR Ligation Due to Independence from Endosome-Mediated IRF3 Activation [CLINICAL AND HUMAN IMMUNOLOGY]
shingle_title_2 Type 1 IFN Induction by Cytosolic Nucleic Acid Is Intact in Neonatal Mononuclear Cells, Contrasting Starkly with Neonatal Hyporesponsiveness to TLR Ligation Due to Independence from Endosome-Mediated IRF3 Activation [CLINICAL AND HUMAN IMMUNOLOGY]
shingle_title_3 Type 1 IFN Induction by Cytosolic Nucleic Acid Is Intact in Neonatal Mononuclear Cells, Contrasting Starkly with Neonatal Hyporesponsiveness to TLR Ligation Due to Independence from Endosome-Mediated IRF3 Activation [CLINICAL AND HUMAN IMMUNOLOGY]
shingle_title_4 Type 1 IFN Induction by Cytosolic Nucleic Acid Is Intact in Neonatal Mononuclear Cells, Contrasting Starkly with Neonatal Hyporesponsiveness to TLR Ligation Due to Independence from Endosome-Mediated IRF3 Activation [CLINICAL AND HUMAN IMMUNOLOGY]
timestamp 2025-06-30T23:36:22.542Z
titel Type 1 IFN Induction by Cytosolic Nucleic Acid Is Intact in Neonatal Mononuclear Cells, Contrasting Starkly with Neonatal Hyporesponsiveness to TLR Ligation Due to Independence from Endosome-Mediated IRF3 Activation [CLINICAL AND HUMAN IMMUNOLOGY]
titel_suche Type 1 IFN Induction by Cytosolic Nucleic Acid Is Intact in Neonatal Mononuclear Cells, Contrasting Starkly with Neonatal Hyporesponsiveness to TLR Ligation Due to Independence from Endosome-Mediated IRF3 Activation [CLINICAL AND HUMAN IMMUNOLOGY]
topic WW-YZ
uid ipn_articles_6315483