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Chapter 13.1 - Fetal infections

Immune responses to congenital infections

from Section 2 - Fetal disease

Published online by Cambridge University Press:  05 February 2013

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
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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.

Type
Chapter
Information
Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
, pp. 200 - 207
Publisher: Cambridge University Press
Print publication year: 2012

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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

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