TLR Responses in Preterm and Term Infant Cord Blood Mononuclear Cells

Anderson, Jeremy; Bender, Georgia; Minh Thang, Cao; Quang Thanh, Le; Thi Trang Dai, Vo; Van Thanh, Phan; Thi Hong Nhu, Bui; Ngoc Xuan Trang, Do; Thi Phuong Trinh, Phan; Vu Thuong, Nguyen; Trong Toan, Nguyen; Mulholland, Kim; Pellicci, Daniel G.; Anh Ha Do, Lien; Licciardi, Paul V.

doi:10.3390/pathogens12040596

Open AccessArticle

TLR Responses in Preterm and Term Infant Cord Blood Mononuclear Cells

by

Jeremy Anderson

^1,2,*

,

Georgia Bender

^1,2

,

Cao Minh Thang

³,

Le Quang Thanh

⁴,

Vo Thi Trang Dai

³,

Phan Van Thanh

³

,

Bui Thi Hong Nhu

⁴,

Do Ngoc Xuan Trang

⁴,

Phan Thi Phuong Trinh

⁴,

Nguyen Vu Thuong

⁴,

Nguyen Trong Toan

⁴,

Kim Mulholland

^1,2,5,

Daniel G. Pellicci

^1,6

,

Lien Anh Ha Do

^1,2,†

and

Paul V. Licciardi

^1,2,*,†

¹

Murdoch Children’s Research Institute, Melbourne, VIC 3052, Australia

²

Department of Paediatrics, University of Melbourne, Melbourne, VIC 3010, Australia

³

Pasteur Institute of Ho Chi Minh City, Ho Chi Minh City 72408, Vietnam

⁴

Tu Du Hospital, Ho Chi Minh City 700000, Vietnam

⁵

Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK

⁶

Department of Microbiology and Immunology, University of Melbourne, Melbourne, VIC 3010, Australia

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Pathogens 2023, 12(4), 596; https://doi.org/10.3390/pathogens12040596

Submission received: 23 February 2023 / Revised: 12 April 2023 / Accepted: 13 April 2023 / Published: 14 April 2023

(This article belongs to the Special Issue Pathogenesis, Treatment and Prevention of Respiratory Viral Infections)

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Abstract

Preterm infants are more susceptible to severe bacterial and viral infectious diseases than their full-term counterparts. A major contributor to this increased susceptibility may be due to differences in their ability to respond to pathogens. While studies have demonstrated altered bacterial Toll-like receptor (TLR) responses, there is limited data on viral TLR responses in preterm infants. In this study, cord blood mononuclear cells (CBMCs) from 10 moderately preterm (30.4–34.1 wGA), 10 term (37–39.5 wGA) infants, and 5 adults were stimulated with TLR2 (lipoteichoic acid), TLR3 (poly I:C), TLR4 (lipopolysaccharide), TLR7/8 (R848), and TLR9 (CpG-ODN 2216) agonists. Following stimulation, the cellular response was measured by intracellular flow cytometry to detect cell-specific NF-κB (as a marker of the inflammatory response), and multiplex assays were used to measure the cytokine response. This study found that preterm and term infants exhibit very similar baseline TLR expression. In response to both bacterial and viral TLR agonists comparing cell-specific NF-κB activation, preterm infants exhibited increased monocyte activation following LTA stimulation; however, no other differences were observed. Similarly, no difference in cytokine response was observed following stimulation with TLRs. However, a stronger correlation between NF-κB activation and cytokine responses was observed in term infants following poly I:C and R848 stimulation compared to preterm infants. In contrast, despite similar TLR expression, adults produced higher levels of IFN-α following R848 stimulation compared to preterm and term infants. These findings suggest preterm and term infants have a similar capacity to respond to both bacterial and viral TLR agonists. As preterm infants are more likely to develop severe infections, further research is required to determine the immunological factors that may be driving this and develop better interventions for this highly vulnerable group.

Keywords: infant; preterm; TLR; inflammation; immune response

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MDPI and ACS Style

Anderson, J.; Bender, G.; Minh Thang, C.; Quang Thanh, L.; Thi Trang Dai, V.; Van Thanh, P.; Thi Hong Nhu, B.; Ngoc Xuan Trang, D.; Thi Phuong Trinh, P.; Vu Thuong, N.; et al. TLR Responses in Preterm and Term Infant Cord Blood Mononuclear Cells. Pathogens 2023, 12, 596. https://doi.org/10.3390/pathogens12040596

AMA Style

Anderson J, Bender G, Minh Thang C, Quang Thanh L, Thi Trang Dai V, Van Thanh P, Thi Hong Nhu B, Ngoc Xuan Trang D, Thi Phuong Trinh P, Vu Thuong N, et al. TLR Responses in Preterm and Term Infant Cord Blood Mononuclear Cells. Pathogens. 2023; 12(4):596. https://doi.org/10.3390/pathogens12040596

Chicago/Turabian Style

Anderson, Jeremy, Georgia Bender, Cao Minh Thang, Le Quang Thanh, Vo Thi Trang Dai, Phan Van Thanh, Bui Thi Hong Nhu, Do Ngoc Xuan Trang, Phan Thi Phuong Trinh, Nguyen Vu Thuong, and et al. 2023. "TLR Responses in Preterm and Term Infant Cord Blood Mononuclear Cells" Pathogens 12, no. 4: 596. https://doi.org/10.3390/pathogens12040596

APA Style

Anderson, J., Bender, G., Minh Thang, C., Quang Thanh, L., Thi Trang Dai, V., Van Thanh, P., Thi Hong Nhu, B., Ngoc Xuan Trang, D., Thi Phuong Trinh, P., Vu Thuong, N., Trong Toan, N., Mulholland, K., Pellicci, D. G., Anh Ha Do, L., & Licciardi, P. V. (2023). TLR Responses in Preterm and Term Infant Cord Blood Mononuclear Cells. Pathogens, 12(4), 596. https://doi.org/10.3390/pathogens12040596

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TLR Responses in Preterm and Term Infant Cord Blood Mononuclear Cells

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