Differential antibacterial control by neutrophil subsets

Abstract

Key Points Neutrophil subsets circulating during acute inflammation are characterized by differential bacterial containment capacity. Adequate antimicrobial containment is associated with profound phagosomal acidification yet independent of reactive oxygen species.

Single-cell transcriptome profiling reveals neutrophil heterogeneity and orchestrated maturation during homeostasis and bacterial infection

“…This study generated the first comprehensive single-cell RNA-seq map of neutrophils under physiological conditions and during bacterial infection. A number of neutrophil subpopulations have previously been identified through functional and phenotypic associations in various models, including but are not limited to human CD177 + (Hu et al, 2009;Silvestre-Roig et al, 2016;Wu et al, 2016;Zhou et al, 2018), olfactomedin-4 + (OLFM4) (Clemmensen et al, 2012), TCR-expressing (Puellmann et al, 2006), CD49d + VEGFR1 high CXCR4 high angiogenic (Christoffersson et al, 2012;Massena et al, 2015), CD63 + (Tirouvanziam et al, 2008), IL-13 + (Chen et al, 2014), CD49 + (Cheung et al, 2010;Tsuda et al, 2004), IL-17producing (Taylor et al, 2014), CD62L dim /CD16 bright and CD62L bright /CD16 dim (Pillay et al, 2012), immunosuppressive CD11c bright CD62L dim CD11b bright CD16 bright (Pillay et al, 2012), CD16 dim banded (Leliefeld et al, 2018), CD62L dim (Tak et al, 2017), mature CD10 + and immature CD10 - (Marini et al, 2017), and tumor- Neutrophils are now known to be important in cancer. Two tumor-associated neutrophil (TAN) subpopulations are present in tumors: pro-inflammatory antitumorigenic N1 neutrophils and pro-tumorigenic N2 neutrophils (Fridlender et al, 2009;Giese et al, 2019;Sionov et al, 2015).…”

Neutrophil Diversity in Health and Disease

“…Humans Mobilization of immature CD66b + CD10 − neutrophils into the circulation (known as the 'left shift') is a well-characterized phenomenon that takes place as a consequence of emergency granulopoiesis [31], either artificially induced [e.g., by lipopolysaccharide (LPS) or G-CSF administration] or disease-associated (e.g., sepsis, infection, cancer). The renewed interest in immature CD66b + CD10 − neutrophils comes from recent evidence showing that these cells, despite their 'immature state', can perform innate immune functions (e.g., chemotaxis and antimicrobial defense) [54,60,61], as well as displaying functional plasticity and immunoregulatory properties (e.g., modulation of proliferation and cytokine production by CD4 + and CD8 + T cells) [62][63][64][65]. Whether immature neutrophils represent a distinct neutrophil subpopulation remains an open question.…”

Immature Neutrophils Released in Acute Inflammation Exhibit Efficient Migration despite Incomplete Segmentation of the Nucleus

“…The differences in proteomic profile could not be explained by neutrophil activation, suggesting the CD62L low neutrophils stem from a different lineage than the CD62L high neutrophils (6). Furthermore, the sorted subsets have repeatedly been demonstrated to differ not only in phenotype (5)(6)(7)(8) but also in function (3,5,7,9). Notably, the hypersegmented CD62L low neutrophil subset has a lower antibacterial capacity than normally segmented CD16 high CD62L high neutrophils (3).…”

“…However, circulatory banded neutrophils were recently shown to have superior antibacterial capacity in vitro, despite their immature morphology (3). This surprising result makes for an attractive concept in which banded neutrophils are not released as bystanders but are deliberately released as cells highly adept at pathogen killing.…”