Fetal infections

Ariane Huygens; Arnaud Marchant

doi:10.1017/CBO9780511997778.024

Chapter 13.1 - Fetal infections

Immune responses to congenital infections

from Section 2 - Fetal disease

Published online by Cambridge University Press: 05 February 2013

Ariane Huygens and

Edited by

Anthony Johnson and

Mark D. Kilby: Affiliation:
Department of Fetal Medicine, University of Birmingham
Anthony Johnson: Affiliation:
Baylor College of Medicine, Texas
Dick Oepkes: Affiliation:
Department of Obstetrics, Leiden University Medical Center

Book contents

Get access

Summary

Introduction

The immune system of the fetus normally develops in a sterile environment. This developmental process prepares the fetus for the challenge of controlling a large diversity of infectious pathogens after birth. Following congenital infections with viruses, bacteria, or protozoans, the fetal immune system is challenged to generate anti-microbial effector functions while it is still primarily controlled by its developmental program. The immune system of the fetus has long been considered as non-reactive or prone to tolerance to foreign antigens. Recent clinical studies have demonstrated that immune effector functions can develop during fetal life. This chapter first provides an overview of the immune system and describes current knowledge of its development during fetal life. The capacity of the fetal immune system to respond to infectious pathogens is then summarized, focusing on the most studied congenital infections.

The immune system at a glance

The immune system is composed of different cell types having specific and inter-related functions. In tissues, immune cells like macrophages and dendritic cells (DCs) express specific receptors, such as Toll-like receptors (TLRs), allowing them to recognize molecules called pathogen-associated-molecular-patterns (PAMPs) that are specifically expressed by pathogens. The interaction with PAMPs activates cells to produce inflammatory cytokines attracting other immune cells such as neutrophils and monocytes to the site of infection. Neutrophils are mainly involved in the phagocytosis and the intracellular killing of pathogens. Monocytes differentiate into macrophages and DCs which have phagocytic properties and activate T lymphocytes.

Keywords

toll-like receptors fetal T lymphocytes infectious microorganisms placenta fetal immune system dendritic cells congenital infections

Type: Chapter
Information: Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
, pp. 200 - 207

DOI: https://doi.org/10.1017/CBO9780511997778.024 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

O’Shea, JJ, Paul, WE. Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 2010; 327(5969):1098–102.Google Scholar

Billingham, RE, Brent, L, Medawar, PB. Actively acquired tolerance of foreign cells. Nature 1953;172(4379):603–6.Google Scholar

Adkins, B, Leclerc, C, Marshall-Clarke, S. Neonatal adaptive immunity comes of age. Nat Rev Immunol 2004;4(7):553–64.Google Scholar

Sarzotti, M, Robbins, DS, Hoffman, PM. Induction of protective CTL responses in newborn mice by a murine retrovirus. Science 1996;271(5256):1726–8.Google Scholar

Ridge, JP, Fuchs, EJ, Matzinger, P. Neonatal tolerance revisited: turning on newborn T cells with dendritic cells. Science 1996;271(5256):1723–6.Google Scholar

Forsthuber, T, Yip, HC, Lehmann, PV. Induction of TH1 and TH2 immunity in neonatal mice. Science 1996;271(5256):1728–30.Google Scholar

Marchant, A, Goldman, M. T cell-mediated immune responses in human newborns: ready to learn? Clin Exp Immunol 2005;141(1):10–18.Google Scholar

Tavian, M, Peault, B. Embryonic development of the human hematopoietic system. Int J Dev Biol 2005;49(2–3):243–50.Google Scholar

Lewis, DB, Wilson, CB. Developmental immunology and role of host defenses in fetal and neonatal susceptibility to infection. In: Remington, JS Klein, JO, Wilson, CB, Nizet, V, Maldonado, YA, eds. Infectious Diseases of the Fetus and Newborn Infant. Philadelphia, Elsevier Saunders. 2011; 80–191.

Goriely, S, Goldman, M. From tolerance to autoimmunity: is there a risk in early life vaccination? J Comp Pathol 2007;137 Suppl 1:S57–61.Google Scholar

Salio, M, Dulphy, N, Renneson, J, et al. Efficient priming of antigen-specific cytotoxic T lymphocytes by human cord blood dendritic cells. Int Immunol 2003;15(10):1265–73.Google Scholar

White, GP, Watt, PM, Holt, BJ, Holt, PG. Differential patterns of methylation of the IFN-gamma promoter at CpG and non-CpG sites underlie differences in IFN-gamma gene expression between human neonatal and adult CD45RO- T cells. J Immunol 2002;168(6):2820–7.Google Scholar

Suryani, S, Fulcher, DA, Santner-Nanan, B, et al. Differential expression of CD21 identifies developmentally and functionally distinct subsets of human transitional B cells. Blood 2010;115(3):519–29.Google Scholar

Michaelsson, J, Mold, JE, McCune, JM, Nixon, DF. Regulation of T cell responses in the developing human fetus. J Immunol 2006;176(10):5741–8.Google Scholar

Mold, JE, Michaelsson, J, Burt, TD, et al. Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science 2008;322(5907):1562–5.Google Scholar

Maldonado, YA, Nizet, V, Klein, JO, Remington, JS, Wilson, CB. Current concepts of infection of the fetus and newborn infant. In: Remington, JS, Klein, JO, Wilson, CB, Nizet, V, Maldonado, YA, eds. Infectious Diseases of the Fetus and Newborn Infant. Philadelphia, Elsevier Saunders. 2011; 2–23.

Marchant, A, Appay, V, Van Der Sande, M, et al. Mature CD8(+) T lymphocyte response to viral infection during fetal life. J Clin Invest 2003;111(11):1747–55.Google Scholar

Pedron, B, Guerin, V, Jacquemard, F, et al. Comparison of CD8+ T cell responses to cytomegalovirus between human fetuses and their transmitter mothers. J Infect Dis 2007;196(7):1033–43.Google Scholar

Gibson, L, Dooley, S, Trzmielina, S, et al. Cytomegalovirus (CMV) IE1- and pp65-specific CD8+ T cell responses broaden over time after primary CMV infection in infants. J Infect Dis 2007;195(12):1789–98.Google Scholar

Gibson, L, Piccinini, G, Lilleri, D, et al. Human cytomegalovirus proteins pp65 and immediate early protein 1 are common targets for CD8+ T cell responses in children with congenital or postnatal human cytomegalovirus infection. J Immunol 2004;172(4):2256–64.Google Scholar

Miles, DJ, van der Sande, M, Jeffries, D, et al. Cytomegalovirus infection in Gambian infants leads to profound CD8 T-cell differentiation. J Virol 2007;81(11):5766–76.Google Scholar

Vermijlen, D, Brouwer, M, Donner, C, et al. Human cytomegalovirus elicits fetal gammadelta T cell responses in utero. J Exp Med 2010;207(4):807–21.Google Scholar

Pass, RF, Stagno, S, Britt, WJ, Alford, CA. Specific cell-mediated immunity and the natural history of congenital infection with cytomegalovirus. J Infect Dis 1983;148(6):953–61.Google Scholar

Starr, SE, Tolpin, MD, Friedman, HM, Paucker, K, Plotkin, SA. Impaired cellular immunity to cytomegalovirus in congenitally infected children and their mothers. J Infect Dis 1979;140(4):500–5.Google Scholar

Tu, W, Chen, S, Sharp, M, et al. Persistent and selective deficiency of CD4+ T cell immunity to cytomegalovirus in immunocompetent young children. J Immunol 2004;172(5):3260–7.Google Scholar

Renneson, J, Dutta, B, Goriely, S, et al. IL-12 and type I IFN response of neonatal myeloid DC to human CMV infection. Eur J Immunol 2009;39(10):2789–99.Google Scholar

Shetty, AK, Maldonado, YA. Human immunodeficiency virus/acquired immunodeficiency syndrome in the infant. In: Remington, JS, Klein, JO, Wilson, CB, Nizet, V, Maldonado, YA, eds. Infectious Diseases of the Fetus and Newborn Infant. Philadelphia, Elsevier Saunders. 2011; 622–60.

Luzuriaga, K, Holmes, D, Hereema, A, et al. HIV-1-specific cytotoxic T lymphocyte responses in the first year of life. J Immunol 1995;154(1):433–43.Google Scholar

Thobakgale, CF, Ramduth, D, Reddy, S, et al. Human immunodeficiency virus-specific CD8+ T-cell activity is detectable from birth in the majority of in utero-infected infants. J Virol 2007;81(23):12775–84.Google Scholar

Lohman, BL, Slyker, JA, Richardson, BA, et al. Longitudinal assessment of human immunodeficiency virus type 1 (HIV-1)-specific gamma interferon responses during the first year of life in HIV-1-infected infants. J Virol 2005;79(13):8121–30.Google Scholar

Streeck, H, Nixon, DF. T cell immunity in acute HIV-1 infection. J Infect Dis 2010;202 Suppl 2:S302–8.Google Scholar

Voelkerding, KV, Sandhaus, LM, Belov, L, et al. Clonal B-cell proliferation in an infant with congenital HIV infection and immune thrombocytopenia. Am J Clin Pathol 1988;90(4):470–4.Google Scholar

Pugatch, D, Sullivan, JL, Pikora, CA, Luzuriaga, K. Delayed generation of antibodies mediating human immunodeficiency virus type 1-specific antibody-dependent cellular cytotoxicity in vertically infected infants. WITS Study Group. Women and Infants Transmission Study. J Infect Dis 1997;176(3):643–8.Google Scholar

Munoz, M, Liesenfeld, O, Heimesaat, MM. Immunology of Toxoplasma gondii. Immunol Rev 2011;240(1):269–85.Google Scholar

Fatoohi, AF, Cozon, GJ, Wallon, M, et al. Cellular immunity to Toxoplasma gondii in congenitally infected newborns and immunocompetent infected hosts. Eur J Clin Microbiol Infect Dis 2003;22(3):181–4.Google Scholar

Ciardelli, L, Meroni, V, Avanzini, MA, et al. Early and accurate diagnosis of congenital toxoplasmosis. Pediatr Infect Dis J 2008;27(2):125–9.Google Scholar

Chapey, E, Wallon, M, Debize, G, Rabilloud, M, Peyron, F. Diagnosis of congenital toxoplasmosis by using a whole-blood gamma interferon release assay. J Clin Microbiol 2010;48(1):41–5.Google Scholar

Guglietta, S, Beghetto, E, Spadoni, A, et al. Age-dependent impairment of functional helper T cell responses to immunodominant epitopes of Toxoplasma gondii antigens in congenitally infected individuals. Microbes Infect 2007;9(2):127–33.Google Scholar

McLeod, R, Beem, MO, Estes, RG. Lymphocyte anergy specific to Toxoplasma gondii antigens in a baby with congenital toxoplasmosis. J Clin Lab Immunol 1985;17(3):149–53.Google Scholar

McLeod, R, Mack, DG, Boyer, K, et al. Phenotypes and functions of lymphocytes in congenital toxoplasmosis. J Lab Clin Med 1990;116(5):623–35.Google Scholar

Hara, T, Ohashi, S, Yamashita, Y, et al. Human V delta 2+ gamma delta T-cell tolerance to foreign antigens of Toxoplasma gondii. Proc Natl Acad Sci U S A 1996;93(10):5136–40.Google Scholar

Maldonado, YA. Less common protozoan and helminth infections. In: Remington, JS, Klein, JO, Wilson, CB, Nizet, V, Maldonado, YA, eds. Infectious Diseases of the Fetus and Newborn Infant. Philadelphia, Elsevier Saunders. 2011; 1042–54.

Hermann, E, Truyens, C, Alonso-Vega, C, et al. Human fetuses are able to mount an adultlike CD8 T-cell response. Blood 2002;100(6):2153–8.Google Scholar

Hermann, E, Alonso-Vega, C, Berthe, A, et al. Human congenital infection with Trypanosoma cruzi induces phenotypic and functional modifications of cord blood NK cells. Pediatr Res 2006;60(1):38–43.Google Scholar

Rodriguez, P, Truyens, C, Alonso-Vega, C, et al. [Serum levels for IgM and IgA antibodies to anti-trypanosoma cruzi in samples of blood from newborns from mothers with positive serology for Chagas disease]. Rev Soc Bras Med Trop 2005;38 Suppl 2:62–4.Google Scholar

Book contents

Chapter 13.1 - Fetal infections

Summary

Keywords

Access options

References

Save book to Kindle

Save book to Dropbox

Save book to Google Drive