Microbial exposure during early human development primes fetal immune cells

Archita Mishra; Ghee Chuan Lai; Leong Jing Yao; Thet Tun Aung; Noam Shental; Aviva Rotter-Maskowitz; Edwin Shepherdson; Gurmit Singh Naranjan Singh; Rhea Pai; Adhika Shanti; Regina Men Men Wong; Andrea Lee; Costerwell Khyriem; Charles Antoine Dutertre; Svetoslav Chakarov; K.G Srinivasan; Nurhidaya Binte Shadan; Xiao-Meng Zhang; Shabnam Khalilnezhad; Fabien Cottier; Alrina Shin Min Tan; Gillian Low; Phyllis Chen; Yiping Fan; Pei Xiang Hor; Avery Khoo May Lee; Mahesh Choolani; David Vermijlen; Ankur Sharma; Garold Fuks; Ravid Straussman; Norman Pavelka; Benoit Malleret; Naomi McGovern; Salvatore Albani; Jerry Kok Yen Chan; Florent Ginhoux

doi:https://doi.org/10.1016/j.cell.2021.04.039

Microbial exposure during early human development primes fetal immune cells

Archita Mishra, Ghee Chuan Lai, Leong Jing Yao, Thet Tun Aung, Noam Shental, Aviva Rotter-Maskowitz, Edwin Shepherdson, Gurmit Singh Naranjan Singh, Rhea Pai, Adhika Shanti, Regina Men Men Wong, Andrea Lee, Costerwell Khyriem, Charles Antoine Dutertre, Svetoslav Chakarov, K.G Srinivasan, Nurhidaya Binte Shadan, Xiao-Meng Zhang, Shabnam Khalilnezhad, Fabien CottierAlrina Shin Min Tan, Gillian Low, Phyllis Chen, Yiping Fan, Pei Xiang Hor, Avery Khoo May Lee, Mahesh Choolani, David Vermijlen, Ankur Sharma, Garold Fuks, Ravid Straussman, Norman Pavelka, Benoit Malleret, Naomi McGovern, Salvatore Albani, Jerry Kok Yen Chan, Florent Ginhoux

Weizmann Institute of Science, Open University of Israel

Research output: Contribution to journal › Article › peer-review

Abstract

The human fetal immune system begins to develop early during gestation; however, factors responsible for fetal immune-priming remain elusive. We explored potential exposure to microbial agents in utero and their contribution toward activation of memory T cells in fetal tissues. We profiled microbes across fetal organs using 16S rRNA gene sequencing and detected low but consistent microbial signal in fetal gut, skin, placenta, and lungs in the 2 ^nd trimester of gestation. We identified several live bacterial strains including Staphylococcus and Lactobacillus in fetal tissues, which induced in vitro activation of memory T cells in fetal mesenteric lymph node, supporting the role of microbial exposure in fetal immune-priming. Finally, using SEM and RNA-ISH, we visualized discrete localization of bacteria-like structures and eubacterial-RNA within 14 ^th weeks fetal gut lumen. These findings indicate selective presence of live microbes in fetal organs during the 2 ^nd trimester of gestation and have broader implications toward the establishment of immune competency and priming before birth.

Original language	English
Pages (from-to)	3394-3409.e20
Journal	Cell
Volume	184
Issue number	13
DOIs	https://doi.org/10.1016/j.cell.2021.04.039
State	Published - 24 Jun 2021

Keywords

Tem
Treg
bacteria
fetal Development
fetal immunity
immune memory
immune priming
microbes
microbiome

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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https://doi.org/10.1016/j.cell.2021.04.039License: CC BY

Cite this

Mishra, A., Lai, G. C., Yao, L. J., Aung, T. T., Shental, N., Rotter-Maskowitz, A., Shepherdson, E., Singh, G. S. N., Pai, R., Shanti, A., Wong, R. M. M., Lee, A., Khyriem, C., Dutertre, C. A., Chakarov, S., Srinivasan, K. G., Shadan, N. B., Zhang, X-M., Khalilnezhad, S., ... Ginhoux, F. (2021). Microbial exposure during early human development primes fetal immune cells. Cell, 184(13), 3394-3409.e20. https://doi.org/10.1016/j.cell.2021.04.039

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title = "Microbial exposure during early human development primes fetal immune cells",

abstract = "The human fetal immune system begins to develop early during gestation; however, factors responsible for fetal immune-priming remain elusive. We explored potential exposure to microbial agents in utero and their contribution toward activation of memory T cells in fetal tissues. We profiled microbes across fetal organs using 16S rRNA gene sequencing and detected low but consistent microbial signal in fetal gut, skin, placenta, and lungs in the 2 nd trimester of gestation. We identified several live bacterial strains including Staphylococcus and Lactobacillus in fetal tissues, which induced in vitro activation of memory T cells in fetal mesenteric lymph node, supporting the role of microbial exposure in fetal immune-priming. Finally, using SEM and RNA-ISH, we visualized discrete localization of bacteria-like structures and eubacterial-RNA within 14 th weeks fetal gut lumen. These findings indicate selective presence of live microbes in fetal organs during the 2 nd trimester of gestation and have broader implications toward the establishment of immune competency and priming before birth.",

keywords = "Tem, Treg, bacteria, fetal Development, fetal immunity, immune memory, immune priming, microbes, microbiome",

author = "Archita Mishra and Lai, {Ghee Chuan} and Yao, {Leong Jing} and Aung, {Thet Tun} and Noam Shental and Aviva Rotter-Maskowitz and Edwin Shepherdson and Singh, {Gurmit Singh Naranjan} and Rhea Pai and Adhika Shanti and Wong, {Regina Men Men} and Andrea Lee and Costerwell Khyriem and Dutertre, {Charles Antoine} and Svetoslav Chakarov and K.G Srinivasan and Shadan, {Nurhidaya Binte} and Xiao-Meng Zhang and Shabnam Khalilnezhad and Fabien Cottier and Tan, {Alrina Shin Min} and Gillian Low and Phyllis Chen and Yiping Fan and Hor, {Pei Xiang} and Lee, {Avery Khoo May} and Mahesh Choolani and David Vermijlen and Ankur Sharma and Garold Fuks and Ravid Straussman and Norman Pavelka and Benoit Malleret and Naomi McGovern and Salvatore Albani and Chan, {Jerry Kok Yen} and Florent Ginhoux",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = jun,

day = "24",

doi = "https://doi.org/10.1016/j.cell.2021.04.039",

language = "الإنجليزيّة",

volume = "184",

pages = "3394--3409.e20",

journal = "Cell",

issn = "0092-8674",

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Mishra, A, Lai, GC, Yao, LJ, Aung, TT, Shental, N, Rotter-Maskowitz, A, Shepherdson, E, Singh, GSN, Pai, R, Shanti, A, Wong, RMM, Lee, A, Khyriem, C, Dutertre, CA, Chakarov, S, Srinivasan, KG, Shadan, NB, Zhang, X-M, Khalilnezhad, S, Cottier, F, Tan, ASM, Low, G, Chen, P, Fan, Y, Hor, PX, Lee, AKM, Choolani, M, Vermijlen, D, Sharma, A, Fuks, G, Straussman, R, Pavelka, N, Malleret, B, McGovern, N, Albani, S, Chan, JKY & Ginhoux, F 2021, 'Microbial exposure during early human development primes fetal immune cells', Cell, vol. 184, no. 13, pp. 3394-3409.e20. https://doi.org/10.1016/j.cell.2021.04.039

TY - JOUR

T1 - Microbial exposure during early human development primes fetal immune cells

AU - Mishra, Archita

AU - Lai, Ghee Chuan

AU - Yao, Leong Jing

AU - Aung, Thet Tun

AU - Shental, Noam

AU - Rotter-Maskowitz, Aviva

AU - Shepherdson, Edwin

AU - Singh, Gurmit Singh Naranjan

AU - Pai, Rhea

AU - Shanti, Adhika

AU - Wong, Regina Men Men

AU - Lee, Andrea

AU - Khyriem, Costerwell

AU - Dutertre, Charles Antoine

AU - Chakarov, Svetoslav

AU - Srinivasan, K.G

AU - Shadan, Nurhidaya Binte

AU - Zhang, Xiao-Meng

AU - Khalilnezhad, Shabnam

AU - Cottier, Fabien

AU - Tan, Alrina Shin Min

AU - Low, Gillian

AU - Chen, Phyllis

AU - Fan, Yiping

AU - Hor, Pei Xiang

AU - Lee, Avery Khoo May

AU - Choolani, Mahesh

AU - Vermijlen, David

AU - Sharma, Ankur

AU - Fuks, Garold

AU - Straussman, Ravid

AU - Pavelka, Norman

AU - Malleret, Benoit

AU - McGovern, Naomi

AU - Albani, Salvatore

AU - Chan, Jerry Kok Yen

AU - Ginhoux, Florent

PY - 2021/6/24

Y1 - 2021/6/24

N2 - The human fetal immune system begins to develop early during gestation; however, factors responsible for fetal immune-priming remain elusive. We explored potential exposure to microbial agents in utero and their contribution toward activation of memory T cells in fetal tissues. We profiled microbes across fetal organs using 16S rRNA gene sequencing and detected low but consistent microbial signal in fetal gut, skin, placenta, and lungs in the 2 nd trimester of gestation. We identified several live bacterial strains including Staphylococcus and Lactobacillus in fetal tissues, which induced in vitro activation of memory T cells in fetal mesenteric lymph node, supporting the role of microbial exposure in fetal immune-priming. Finally, using SEM and RNA-ISH, we visualized discrete localization of bacteria-like structures and eubacterial-RNA within 14 th weeks fetal gut lumen. These findings indicate selective presence of live microbes in fetal organs during the 2 nd trimester of gestation and have broader implications toward the establishment of immune competency and priming before birth.

AB - The human fetal immune system begins to develop early during gestation; however, factors responsible for fetal immune-priming remain elusive. We explored potential exposure to microbial agents in utero and their contribution toward activation of memory T cells in fetal tissues. We profiled microbes across fetal organs using 16S rRNA gene sequencing and detected low but consistent microbial signal in fetal gut, skin, placenta, and lungs in the 2 nd trimester of gestation. We identified several live bacterial strains including Staphylococcus and Lactobacillus in fetal tissues, which induced in vitro activation of memory T cells in fetal mesenteric lymph node, supporting the role of microbial exposure in fetal immune-priming. Finally, using SEM and RNA-ISH, we visualized discrete localization of bacteria-like structures and eubacterial-RNA within 14 th weeks fetal gut lumen. These findings indicate selective presence of live microbes in fetal organs during the 2 nd trimester of gestation and have broader implications toward the establishment of immune competency and priming before birth.

KW - Tem

KW - Treg

KW - bacteria

KW - fetal Development

KW - fetal immunity

KW - immune memory

KW - immune priming

KW - microbes

KW - microbiome

UR - http://www.scopus.com/inward/record.url?scp=85108309898&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.cell.2021.04.039

DO - https://doi.org/10.1016/j.cell.2021.04.039

M3 - مقالة

C2 - 34077752

SN - 0092-8674

VL - 184

SP - 3394-3409.e20

JO - Cell

JF - Cell

IS - 13

ER -

Microbial exposure during early human development primes fetal immune cells

Abstract

Keywords

All Science Journal Classification (ASJC) codes

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