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HIV, Cytomegalovirus, and Malaria Infections during Pregnancy Lead to Inflammation and Shifts in Memory B Cell Subsets in Kenyan Neonates

Kee Thai Yeo, Paula Embury, Timothy Anderson, Peter Mungai, Indu Malhotra, Christopher King, James Kazura and Arlene Dent
J Immunol January 23, 2019, ji1801024; DOI: https://doi.org/10.4049/jimmunol.1801024
Kee Thai Yeo
*Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106;
†Department of Pediatrics, Rainbow Babies and Children’s Hospital, Case Western Reserve University, Cleveland, OH 44106; and
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Paula Embury
*Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106;
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Timothy Anderson
*Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106;
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Peter Mungai
*Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106;
‡Division of Vector Borne and Neglected Tropical Diseases, Ministry of Public Health and Sanitation, Nairobi 00200, Kenya
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Indu Malhotra
*Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106;
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Christopher King
*Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106;
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James Kazura
*Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106;
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Arlene Dent
*Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106;
†Department of Pediatrics, Rainbow Babies and Children’s Hospital, Case Western Reserve University, Cleveland, OH 44106; and
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Abstract

Infections during pregnancy can expose the fetus to microbial Ags, leading to inflammation that affects B cell development. Prenatal fetal immune priming may have an important role in infant acquisition of pathogen-specific immunity. We examined plasma proinflammatory biomarkers, the proportions of various B cell subsets, and fetal priming to tetanus vaccination in cord blood from human United States and Kenyan neonates. United States neonates had no identified prenatal infectious exposures, whereas Kenyan neonates examined had congenital CMV or mothers with prenatal HIV or Plasmodium falciparum or no identified infectious exposures. Kenyan neonates had higher levels of IP-10, TNF-α, CRP, sCD14, and BAFF than United States neonates. Among the Kenyan groups, neonates with prenatal infections/infectious exposures had higher levels of cord blood IFN-γ, IL-7, sTNFR1, and sTNFR2 compared with neonates with no infectious exposures. Kenyan neonates had greater proportions of activated memory B cells (MBC) compared with United States neonates. Among the Kenyan groups, HIV-exposed neonates had greater proportions of atypical MBC compared with the other groups. Although HIV-exposed neonates had altered MBC subset distributions, detection of tetanus-specific MBC from cord blood, indicative of fetal priming with tetanus vaccine given to pregnant women, was comparable in HIV-exposed and non–HIV-exposed neonates. These results indicate that the presence of infections during pregnancy induces fetal immune activation with inflammation and increased activated MBC frequencies in neonates. The immunologic significance and long-term health consequences of these differences warrant further investigation.

Footnotes

  • This work was supported by the Center for AIDS Research services of the National Institutes of Health (NIH) P30 AI036219, MH080601 (to Penny Holding), AI064667 (to C.K.), and AI098511 (to A.D.). This publication was made possible by the Clinical and Translational Science Collaborative of Cleveland, Case Western Reserve University/Cleveland Clinic Clinical Translational Science Award UL1TR000439 from the National Center for Advancing Translational Sciences component of the NIH, and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

  • The online version of this article contains supplemental material.

  • Received July 24, 2018.
  • Accepted December 17, 2018.
  • Copyright © 2019 by The American Association of Immunologists, Inc.

This article is distributed under The American Association of Immunologists, Inc., Reuse Terms and Conditions for Author Choice articles.

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The Journal of Immunology: 208 (11)
The Journal of Immunology
Vol. 208, Issue 11
1 Jun 2022
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HIV, Cytomegalovirus, and Malaria Infections during Pregnancy Lead to Inflammation and Shifts in Memory B Cell Subsets in Kenyan Neonates
Kee Thai Yeo, Paula Embury, Timothy Anderson, Peter Mungai, Indu Malhotra, Christopher King, James Kazura, Arlene Dent
The Journal of Immunology January 23, 2019, ji1801024; DOI: 10.4049/jimmunol.1801024

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HIV, Cytomegalovirus, and Malaria Infections during Pregnancy Lead to Inflammation and Shifts in Memory B Cell Subsets in Kenyan Neonates
Kee Thai Yeo, Paula Embury, Timothy Anderson, Peter Mungai, Indu Malhotra, Christopher King, James Kazura, Arlene Dent
The Journal of Immunology January 23, 2019, ji1801024; DOI: 10.4049/jimmunol.1801024
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