Age-dependent differences in efferocytosis determine the outcome of opsonophagocytic protection from invasive pathogens

被引:9
作者
Bee, Gavyn Chern Wei [1 ]
Lokken-Toyli, Kristen L. [1 ]
Yeung, Stephen T. [1 ]
Rodriguez, Lucie [2 ]
Zangari, Tonia [1 ]
Anderson, Exene E. [1 ]
Ghosh, Sourav [3 ,4 ]
Rothlin, Carla V. [3 ,5 ]
Brodin, Petter [2 ]
Khanna, Kamal M. [1 ,6 ,7 ]
Weiser, Jeffrey N. [1 ]
机构
[1] NYU, Grossman Sch Med, Dept Microbiol, New York, NY 10012 USA
[2] Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden
[3] Yale Sch Med, Dept Pharmacol, New Haven, CT USA
[4] Yale Sch Med, Dept Neurol, New Haven, CT USA
[5] Yale Sch Med, Dept Immunobiol, New Haven, CT USA
[6] Imperial Coll London, Dept Immunol & Inflammat, London, England
[7] New York Univ Langone Hlth, Laura & Isaac Perlmutter Canc Ctr, New York, NY USA
基金
瑞典研究理事会; 美国国家卫生研究院;
关键词
TOTAL CELL CONTENT; STREPTOCOCCUS-PNEUMONIAE; APOPTOTIC CELLS; NEUTROPHILS CONTRIBUTE; PHAGOCYTOSIS; COMPLEMENT; MICROBIOTA; RECEPTOR; CAPSULE; PEPTIDOGLYCAN;
D O I
10.1016/j.immuni.2023.03.018
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In early life, susceptibility to invasive infection skews toward a small subset of microbes, whereas other path-ogens associated with diseases later in life, including Streptococcus pneumoniae (Spn), are uncommon among neonates. To delineate mechanisms behind age-dependent susceptibility, we compared age-specific mouse models of invasive Spn infection. We show enhanced CD11b-dependent opsonophagocytosis by neonatal neutrophils improved protection against Spn during early life. The augmented function of neonatal neutrophils was mediated by higher CD11b surface expression at the population level due to dampened ef-ferocytosis, which also resulted in more CD11bhi "aged"neutrophils in peripheral blood. Dampened effero-cytosis during early life could be attributed to the lack of CD169+ macrophages in neonates and reduced sys-temic expressions of multiple efferocytic mediators, including MerTK. On experimentally impairing efferocytosis later in life, CD11bhi neutrophils increased and protection against Spn improved. Our findings reveal how age-dependent differences in efferocytosis determine infection outcome through the modulation of CD11b-driven opsonophagocytosis and immunity.
引用
收藏
页码:1255 / +
页数:20
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