Innate Immune Mechanism of Neutrophil Extracellular Trap Formation is Impaired in at-Risk Term Low Birth Weight Newborns

Abstract

Low birth weight (LBW) is a leading cause of newborn’s mortality however the underlying defects in cellular immunity and immune mechanisms leading to severe neonatal infections in term LBW (tLBW) newborns are not well understood. Neutrophil extracellular traps (NETs), or NETosis, is an innate immune defense mechanism of neutrophils involved in trapping and killing of microbes. The efficiency of NET formation in cord blood derived neutrophils of tLBW and normal birth weight (NBW) newborns in the presence of toll like receptor (TLR) agonist inductions was evaluated. The NET formation was observed to be substantially impaired in tLBW newborns along with NET proteins expression, extracellular deoxyribonucleic acid (DNA) release and reactive oxygen species generation. The placental tissues from tLBW newborns delivery also showed minimal NETosis. These findings suggest impaired NET formation to be an important factor underlying the deficient immune status of tLBW newborns making them susceptible to life- threatening infections.

Graphical Abstract

Keywords:

• low birth weight
• NETosis
• Neutrophil extracellular trap
• placenta
• toll-like receptor

Acknowledgements

We thank Department of Biotechnology, New Delhi, India for providing research fellowship to DD.We gratefully acknowledge the confocal microscope facility of Interdisciplinary School of Life Sciences, scanning electron microscope facility of, Department of Zoology, Center for advance study, flow cytometer facility of Central Discovery Centre, Banaras Hindu University, Varanasi-India.

Authors’ contributions

G.R. conceptualized and designed the study. D.D and V.V.S performed the experiments, and, G.R and D.D analyzed the data, drafted the manuscript. S.K.C. and R.R. carried out the analysis and interpretation of data, reviewed the manuscript. A.K and M.J. provided cord blood samples for the study and did clinical analysis. G.R. critically reviewed and revised the manuscript, provided overall guidance for the project and approved the final manuscript as submitted. All authors approved the final manuscript as submitted and agree to be accountable for related aspects of the work.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by grants from the Department of Biotechnology, New Delhi, India (BT/PR9211/MED/97/128/2013) and University Grants Commission, New Delhi, India (UGC-UPE thrust area program, FA-II/2013-14) to GR.