Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection.
Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection.
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DOI：
10.1038/nature12675
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发表时间：
2013-12-05
期刊：
影响因子：
64.8
通讯作者：
Way, Sing Sing
中科院分区：
文献类型：
--
作者：
Elahi, Shokrollah;Ertelt, James M.;Kinder, Jeremy M.;Jiang, Tony T.;Zhang, Xuzhe;Xin, Lijun;Chaturvedi, Vandana;Strong, Beverly S.;Qualls, Joseph E.;Steinbrecher, Kris A.;Kalfa, Theodosia A.;Shaaban, Aimen F.;Way, Sing Sing
新生儿极易受感染。这种宿主防御的缺陷通常归因于新生儿免疫细胞的不成熟；然而，反应性低下的程度是高度可变的，取决于刺激条件。这些不一致的反应表明，需要对新生儿免疫力受损的原因作出更统一的解释。本研究表明，新生小鼠和人脐带血中生理性富集的CD71+红细胞具有独特的免疫抑制特性。成年细胞产生的先天免疫保护细胞因子在转移到新生小鼠或与新生脾细胞共培养后减少。新生儿CD71+细胞表达精氨酸酶-2，精氨酸酶活性对这些细胞的免疫抑制特性至关重要，因为该酶的分子抑制或补充l-精氨酸会超过免疫抑制。此外，新生小鼠体内CD71+细胞的消融，或随着出生后发育的进展，这些细胞数量的下降与抑制的丧失相似，并恢复了对围产期病原体单核细胞增生李斯特菌和大肠杆菌的抵抗力。然而，CD71+细胞介导的对感染的易感性被CD71+细胞介导的对肠道中异常免疫细胞激活的保护所抵消，肠道中共生微生物的定植在分娩后迅速发生。相反，通过使用抗菌剂或无菌小鼠来避免这种定植会抵消这些保护作用。因此，CD71+细胞抑制了分娩后共生微生物突然定植引起的过度炎症。这一发现挑战了新生儿对感染的易感性反映免疫细胞内在缺陷的观点，而是强调了发育更重要的过程，无意中减轻了先天免疫保护。我们预计这些结果将引发对新生儿免疫抑制需求的重新研究，以及对这一弱势群体增强宿主防御的改进策略。
Newborn infants are highly susceptible to infection. This defect in host defence has generally been ascribed to the immaturity of neonatal immune cells; however, the degree of hyporesponsiveness is highly variable and depends on the stimulation conditions. These discordant responses illustrate the need for a more unified explanation for why immunity is compromised in neonates. Here we show that physiologically enriched CD71+ erythroid cells in neonatal mice and human cord blood have distinctive immunosuppressive properties. The production of innate immune protective cytokines by adult cells is diminished after transfer to neonatal mice or after co-culture with neonatal splenocytes. Neonatal CD71+ cells express the enzyme arginase-2, and arginase activity is essential for the immunosuppressive properties of these cells because molecular inhibition of this enzyme or supplementation with l-arginine overrides immunosuppression. In addition, the ablation of CD71+ cells in neonatal mice, or the decline in number of these cells as postnatal development progresses parallels the loss of suppression, and restored resistance to the perinatal pathogens Listeria monocytogenes and Escherichia coli. However, CD71+ cell-mediated susceptibility to infection is counterbalanced by CD71+ cell-mediated protection against aberrant immune cell activation in the intestine, where colonization with commensal microorganisms occurs swiftly after parturition.Conversely, circumventing such colonization by using antimicrobials or gnotobiotic germ-free mice overrides these protective benefits. Thus, CD71+ cells quench the excessive inflammation induced by abrupt colonization with commensal microorganisms after parturition. This finding challenges the idea that the susceptibility of neonates to infection reflects immune-cell-intrinsic defects and instead highlights processes that are developmentally more essential and inadvertently mitigate innate immune protection. We anticipate that these results will spark renewed investigation into the need for immunosuppression in neonates, as well as improved strategies for augmenting host defence in this vulnerable population.
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影响因子：
2.6
作者：
Camacho-Gonzalez, Andres;Spearman, Paul W.;Stoll, Barbara J.
通讯作者：
Stoll, Barbara J.
影响因子：
4.4
作者：
Morera D;MacKenzie SA
通讯作者：
MacKenzie SA
DOI：
10.4049/jimmunol.0901481
发表时间：
2009-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kollmann TR;Crabtree J;Rein-Weston A;Blimkie D;Thommai F;Wang XY;Lavoie PM;Furlong J;Fortuno ES 3rd;Hajjar AM;Hawkins NR;Self SG;Wilson CB
通讯作者：
Wilson CB
影响因子：
3.1
作者：
Prins, HA;Houdijk, APJ;van Leeuwen, PAM
通讯作者：
van Leeuwen, PAM
影响因子：
64.8
作者：
Maynard, Craig L.;Elson, Charles O.;Hatton, Robin D.;Weaver, Casey T.
通讯作者：
Weaver, Casey T.