Expression of FcRn receptor in placental tissue and its relationship with IgG levels in term and preterm newborns

Lozano, Natalia A.; Lozano, Alejandro; Marini, Vanina; Saranz, Ricardo J; Blumberg, Richard S.; Baker, Kristi; Agresta, María Fernanda; Ponzio, Marina Flavia

doi:10.1111/aji.12972

Cited by 52 publications

(52 citation statements)

References 41 publications

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“…However, given that FcRn expressed on the surface of these cells transcytoses maternal-derived IgG directly into the underlying fetal blood, our identification of FcRn as an echovirus receptor raises the possibility that echoviruses might have higher rates of transplacental transfer than has been previously appreciated. In addition, it should be noted that the highest rates of transplacental IgG transfer occur in the third trimester, with the level of maternalderived IgG greater in the fetus than in the mother (33). Thus, a maternal echovirus infection in the later stages of pregnancy could potentially lead to FcRn-mediated placental infection or transplacental viral transport and expose the fetus to virus before delivery.…”

Section: Discussionmentioning

confidence: 99%

The neonatal Fc receptor is a pan-echovirus receptor

Morosky

Wells

Lemon

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Echoviruses are amongst the most common causative agents of aseptic meningitis worldwide and are particularly devastating in the neonatal population, where they are associated with severe hepatitis, neurological disease, including meningitis and encephalitis, and even death. Here, we identify the neonatal Fc receptor (FcRn) as a pan-echovirus receptor. We show that loss of expression of FcRn or its binding partner beta 2 microglobulin (β2M) renders cells resistant to infection by a panel of echoviruses at the stage of virus attachment, and that a blocking antibody to β2M inhibits echovirus infection in cell lines and in primary human intestinal epithelial cells. We also show that expression of human, but not mouse, FcRn renders nonpermissive human and mouse cells sensitive to echovirus infection and that the extracellular domain of human FcRn directly binds echovirus particles and neutralizes infection. Lastly, we show that neonatal mice expressing human FcRn are more susceptible to echovirus infection by the enteral route. Our findings thus identify FcRn as a pan-echovirus receptor, which may explain the enhanced susceptibility of neonates to echovirus infections.

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Section: Discussionmentioning

confidence: 99%

The neonatal Fc receptor is a pan-echovirus receptor

Morosky

Wells

Lemon

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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show abstract

“…Our identification of FcRn as an echovirus receptor raises the possibility that echoviruses might have higher rates of transplacental transfer than has been appreciated. In addition, it should be noted that the highest rates of transplacental IgG transfer occur in the third trimester, with the level of maternal-derived IgG is greater in the fetus than in the mother (45). Thus, a maternal echovirus infection in the later stages of pregnancy could potentially lead to FcRn-mediated placental infection or transplacental viral transport and expose the fetus to virus prior to delivery.…”

Section: Discussionmentioning

confidence: 99%

The neonatal Fc receptor is a pan-echovirus receptor

Morosky

Evans

Lemon

et al. 2018

Preprint

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52Echoviruses are the main causative agents of aseptic meningitis worldwide and are particularly 53 devastating in the neonatal population, where they are associated with severe hepatitis, 54 neurological disease including meningitis and encephalitis, and even death. Here, we identify the 55 neonatal Fc receptor (FcRn) as a pan-echovirus receptor. We show that loss of expression of 56 FcRn or its binding partner beta 2 microglubulin (b2M) renders human brain microvascular cells 57 resistant to infection by a panel of echoviruses at the stage of virus attachment and that a blocking 58 antibody to b2M inhibit echovirus infection in cell lines and in primary human fetal intestinal 59 epithelial cells. We also show that expression of human, but not mouse, FcRn renders non-60 permissive human and mouse cells sensitive to echovirus infection and that the extracellular 61 domain of human FcRn directly binds echoviral particles and neutralizes infection. Lastly, we 62 show that primary cells isolated from mice that express human FcRn are highly susceptible to 63 echovirus infection. Our findings thus identify FcRn as a pan-echovirus receptor, which may 64 explain the enhanced susceptibility of neonates to echovirus infections. 65 66 Significance 67 68 Echoviruses are associated with aseptic meningitis and induce severe disease, and even death, 69 in neonates and young infants. Here, we identify the neonatal Fc receptor (FcRn) as a pan-70 echovirus receptor. FcRn is expressed on the surface of the human placenta, and throughout life 71 in intestinal enterocytes, liver hepatocytes, and in the microvascular endothelial cells that line the 72 blood-brain barrier. This pattern of expression is consistent with the organ sites targeted by 73 echoviruses in humans, with the primary entry site of infection in the intestinal tract and 74

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“…Los procesos evolutivos han desarrollado mecanismos muy eficientes de transferencia de inmunidad materna con el objetivo de aportar células inmunes y anticuerpos maternos capaces de proteger al recién nacido temporalmente. La transferencia de anticuerpos puede ocurrir a través de la placenta durante el estadio prenatal, vía calostro y leche materna luego del nacimiento, o por ambas vías según la especie 9,13 .…”

Section: Función Inmuneunclassified

“…La respuesta humoral inicial se denomina primaria, caracterizada por un periodo de latencia prolongado, intensidad baja y duración corta, donde predomina el isotipo de inmunoglobulina M (IgM) lo que conlleva a una baja afinidad. Por lo tanto, el recién nacido depende de la transferencia de anticuerpos maternos 12,13 . Ésta, puede ocurrir vía placenta en estadio prenatal, vía calostro y leche materna luego del nacimiento, o por ambas vías, según la especie 9 .…”

Section: Transferencia De Inmunidad Pasivaunclassified

“…En mamíferos el isotipo de Ig predominante a nivel sistémico es la IgG y también es el principal isotipo transferido de la madre a las crías 9 . Los mecanismos de transferencia pueden ser dependientes de la expresión del receptor neonatal Fc (FcRn) que permite el transporte activo de IgG o bien, de un proceso no selectivo de captación de macromoléculas a través de vacuolas de transporte 13,14 . El transporte mediado por el receptor FcRn depende del gradiente de pH, uniéndose la IgG a pH ácido y siendo liberada a pH neutro; esto garantiza la unión a tipos celulares específicos (placenta, glándula mamaria, enterocitos duodenales) y la liberación de IgG en sitios adecuados como el torrente sanguíneo 9,13 .…”

Section: Transferencia De Inmunidad Pasivaunclassified

See 1 more Smart Citation

Estructura de la placenta y su impacto en la transferencia de la inmunidad materno-fetal. revisión en mamíferos domésticos.

Auad¹,

Cerutti²,

Cooper³

et al. 2019

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The placenta is an essential organ for pregnancy in domestic mammals. It is constituted by maternal fetal tissues and fulfills numerous functions: exchange of gases, nutrients and excretion of waste products, prevents the immune system from identifying the embryo as a foreign body and synthesizes hormones and growth factors. There is great structural diversity in placentas of different animal species, and those can be classified in different ways. The most relevant is the macroscopic morphological classification, which is based on the distribution of the placental villi in the corium of the fetus, and the histological, that relies on the number of layers between maternal and fetal blood, determining if there is immunoglobulin (Ig) transfer or it is Revista Methodo: Investigación Aplicada a las Ciencias Biológicas.

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Expression of FcRn receptor in placental tissue and its relationship with IgG levels in term and preterm newborns

Abstract: Our results obtained from clinical samples, were in line with previous descriptions in model systems and confirmed that the IgG transfer from maternal serum to the fetus is positively correlated with FcRn expression in placental tissue throughout gestation.

Cited by 52 publications

References 41 publications

The neonatal Fc receptor is a pan-echovirus receptor

The neonatal Fc receptor is a pan-echovirus receptor

The neonatal Fc receptor is a pan-echovirus receptor

Estructura de la placenta y su impacto en la transferencia de la inmunidad materno-fetal. revisión en mamíferos domésticos.

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