Neonatal macrophages express elevated levels of interleukin-27 that oppose immune responses

被引:48
作者
Kraft, Jennifer D. [1 ]
Horzempa, Joseph [2 ]
Davis, Celestia [3 ,4 ]
Jung, Joo-Yong [1 ]
Pena, Maria Marjorette O. [3 ,4 ]
Robinson, Cory M. [1 ]
机构
[1] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC USA
[2] West Liberty Univ, Dept Nat Sci & Math, West Liberty, WV USA
[3] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA
[4] Univ S Carolina, Ctr Colon Canc Res, Columbia, SC 29208 USA
基金
美国国家卫生研究院;
关键词
interferon-; interleukin-27; macrophages; neonate; T cells; T-HELPER-CELLS; DENDRITIC CELLS; ADAPTIVE IMMUNITY; INTERFERON-GAMMA; IL-27; INNATE; ANTIBODY; WSX-1; PROLIFERATION; INFECTION;
D O I
10.1111/imm.12095
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Microbial infections are a major cause of infant mortality worldwide because of impaired immune defences in this population. The nature of this work was to further understand the mechanistic limitations of the neonatal and infant immune response. Interleukin-27 (IL-27) is a heterodimeric cytokine of the IL-12 family that is produced primarily by antigen-presenting cells and is immunosuppressive toward a variety of immune cell types. We show that IL-27 gene expression is elevated in cord blood-derived macrophages relative to macrophages originating from healthy adults. We also evaluated the duration over which elevated IL-27 gene expression may impact immune responses in mice. Age-dependent analysis of IL-27 gene expression indicated that levels of IL-27 remained significantly elevated throughout infancy and then declined in adult mice. Flow cytometric analysis of intracellular cytokine-stained splenocytes further confirmed these results. Interleukin-27 may be induced during pregnancy to contribute to the immunosuppressive environment at the fetal-maternal interface because we demonstrate dose-responsive gene expression to progesterone in macrophages. Neutralization of IL-27 in neonatal macrophages improved the ability of these cells to limit bacterial replication. Moreover, neutralization of IL-27 during incubation with the Mycobacterium bovis bacillus Calmette-Guerin vaccine augmented the level of interferon-gamma elicited from allogeneic CD4(+) T lymphocytes. This suggests that blocking IL-27 during vaccination and infection may improve immune responses in newborn and infant populations. Furthermore, mice will be a suitable model system to further address these possibilities.
引用
收藏
页码:484 / 493
页数:10
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[41]   Neonatal interleukin-12 capacity is associated with variations in allergen-specific immune responses in the neonatal and postnatal periods [J].
Prescott, SL ;
Taylor, A ;
King, B ;
Dunstan, J ;
Upham, JW ;
Thornton, CA ;
Holt, PG .
CLINICAL AND EXPERIMENTAL ALLERGY, 2003, 33 (05) :566-572
[42]   Interferon-γ/Interleukin-27 Axis Induces Programmed Death Ligand 1 Expression in Monocyte-Derived Dendritic Cells and Restores Immune Tolerance in Central Nervous System Autoimmunity [J].
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Park, Jeongho ;
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Ciric, Bogoljub .
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[43]   Interleukin-27 Enhances the Potential of Reactive Oxygen Species Generation from Monocyte-derived Macrophages and Dendritic cells by Induction of p47phox [J].
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Saito, Yoshiro ;
Poudyal, Deepak ;
Chen, Qian ;
Sui, Hongyan ;
DeRavin, Suk See ;
Imamichi, Hiromi ;
Sato, Toyotaka ;
Kuhns, Douglas B. ;
Noguchi, Noriko ;
Malech, Harry L. ;
Lane, H. Clifford ;
Imamichi, Tomozumi .
SCIENTIFIC REPORTS, 2017, 7
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[45]   The secreted form of p28 subunit of interleukin (IL)-27 inhibits biological functions of IL-27 and suppresses anti-allogeneic immune responses [J].
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[46]   Interleukin-27 gene variant rs153109 is associated with enhanced cytokine serum levels and susceptibility to Behçet’s disease in the Iranian population [J].
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[47]   Circulating interleukin-27 levels in Helicobacter pylori-infected patients with gastric or duodenal ulcers, independent of the bacterial cytotoxin-associated gene A virulence factor [J].
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Nemati, Maryam ;
Rezayati, Mohammad-Taghi .
JOURNAL OF DIGESTIVE DISEASES, 2011, 12 (04) :302-307
[48]   Elevated Interleukin-6 Levels as a Potential Marker of Neonatal Morbidity in Full-term Infants With Polycythemia: A Prospective Study [J].
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[49]   Plasma interleukin-18 levels are a biomarker of innate immune responses that predict and characterize tuberculosis-associated immune reconstitution inflammatory syndrome [J].
Tan, Hong Yien ;
Yong, Yean Kong ;
Andrade, Bruno B. ;
Shankar, Esaki M. ;
Ponnampalavanar, Sasheela ;
Omar, Sharifah F. S. ;
Narendran, Gopalan ;
Kamarulzaman, Adeeba ;
Swaminathan, Soumya ;
Sereti, Irini ;
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[50]   ELEVATED LEVELS OF T-CELL ACTIVATION ANTIGEN CD27 AND INCREASED INTERLEUKIN-4 PRODUCTION IN HUMAN LYMPHATIC FILARIASIS [J].
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SARTONO, E ;
KRUIZE, YCM ;
KURNIAWAN, A ;
VANDERPOUWKRAAN, T ;
VANDERMEIDE, PH ;
SELKIRK, ME ;
PARTONO, F ;
HINTZEN, RQ ;
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