RESUMEN
Resumen La interacción entre la madre y el feto durante el embarazo se ha estudiado exhaustivamente. Una de estas interacciones es el microquimerismo, el cual se caracteriza por un intercambio madre-feto de células y material genético. Adicional a la gestación, la madre hereda más células por medio de la lactancia, donde se transfieren biocomponentes (células, anticuerpos y bacterias comensales) que juegan un papel importante en la adaptación del recién nacido al medio. Las consecuencias de este microquimerismo posparto genera beneficios directos en los primeros meses de vida, previniendo enfermedades e infecciones, induciendo tolerancia a moléculas inocuas, así como favoreciendo el entrenamiento inmunitario del recién nacido, con respuestas dirigidas y beneficios en la vida adulta. Es destacable que el microquimerismo materno podría interpretarse como un legado inmunológico en el neonato, el cual es perdurable para algunos de sus componentes y definitorio en el correcto desarrollo de la progenie.
Abstract The interaction between mother and fetus during pregnancy has been extensively studied. One of these interactions is the microchimerism, which is characterized by a mother-fetus exchange of cells and genetic material. In addition to gestation, the mother inherits more cells through lactation, in which biocomponents (cells, antibodies, and commensal bacteria) that play an important role in the adaptation of the newborn to the environment are transferred. The consequences of this post-partum microchimerism generate direct benefits in the first months of life, preventing diseases and infections, inducing tolerance to innocuous molecules, as well as favoring the immunological training of the newborn, with specialized responses and benefits in adult life. It is noteworthy that maternal microchimerism could be interpreted as an immunological legacy in the neonate, which is lasting for some of its components, and defining in the correct development of the progeny.
RESUMEN
Over the last 20 years, the incidence of vertical HIV transmission has decreased from 25%-42% to less than 1%. Although there are no signs of infection, the health of HIV-exposed uninfected (HEU) infants is notoriously affected during the first months of life, with opportunistic infections being the most common disease. Some studies have reported effects on the vertical transfer of antibodies, but little is known about the subclass distribution of these antibodies. We proposed to evaluate the total IgG concentration and its subclasses in HIV+ mothers and HEU pairs and to determine which maternal factors condition their levels. In this study, plasma from 69 HEU newborns, their mothers, and 71 control pairs was quantified via immunoassays for each IgG isotype. Furthermore, we followed the antibody profile of HEUs throughout the first year of life. We showed that mothers present an antibody profile characterized by high concentrations of IgG1 and IgG3 but reduced IgG2, and HEU infants are born with an IgG subclass profile similar to that of their maternal pair. Interestingly, this passively transferred profile could remain influenced even during their own antibody production in HEU infants, depending on maternal conditions such as CD4+ T-cell counts and maternal antiretroviral treatment. Our findings indicate that HEU infants exhibit an altered IgG subclass profile influenced by maternal factors, potentially contributing to their increased susceptibility to infections.
Asunto(s)
Infecciones por VIH , Lactante , Humanos , Recién Nacido , Inmunoglobulina G , Incidencia , Recuento de Linfocito CD4 , Transmisión Vertical de Enfermedad InfecciosaRESUMEN
Resumen Con la implementación de estrategias de cuidado perinatal, la tasa de transmisión vertical del virus de inmunodeficiencia humana (VIH) ha disminuido considerablemente en el mundo. A pesar de no mostrar cargas virales, los infantes expuestos al VIH no infectados (ENI) cursan en sus primeros meses de vida con mayores tasas de morbimortalidad. Esto se relaciona con enfermedades infecciosas por microorganismos oportunistas y menor respuesta a las vacunas en comparación con infantes sin exposición al virus, lo que sugiere alteraciones en su sistema inmunitario. En esta revisión abordamos diferentes evidencias de alteraciones en las respuestas inmunitarias innatas y adaptativas de infantes ENI que pudieran explicar esta disfuncionalidad inmunitaria. Adicionalmente, este conocimiento ayuda a entender cómo se desarrolla el sistema inmunitario desde los primeros momentos de gestación que servirán para encontrar alternativas de manejo y terapias para el bienestar de los infantes con esta condición.
Abstract With the implementation of perinatal care strategies, the rate of vertical transmission of human immunodeficiency virus (HIV) has decreased considerably worldwide. Despite the absence of viral loads, infants exposed to HIV not infected during gestation have higher morbidity and mortality rates. This is found to be related to infectious diseases by opportunistic microorganisms and lower response to vaccines in their first months of life compared to non-HIV exposed infants, suggesting alterations in their immune system. In this review we address different evidence of alterations in the innate and adaptive immune responses of HIV exposed infants that could explain their immune dysfunctionality. Additionally, this knowledge helps to understand how the immune system develops from the early stages of gestation and will serve to find management alternatives and therapies for the welfare of the infants with this condition.
RESUMEN
INTRODUCTION: HIV-exposed uninfected (HEU) newborns suffer from higher risks of opportunistic infections during the first months of life compared to HIV-unexposed uninfected (HUU) newborns. Alterations in thymic mass, amounts of T helper (Th) cells, T-cell receptor diversity, and activation markers have been found in HEU newborns, suggesting alterations in T cell ontogeny and differentiation. However, little is known about the ability of these cells to produce specialized Th responses from CD4+ T cells. METHOD: To characterize the Th cell profile, we evaluated the frequency of Th1 (CD183+ CD194- CD196- /CXCR3+ CCR4- CCR6- ), Th2 (CD183- CD194+ CD196- /CXCR3- CCR4+ CCR6- ), Th17 (CD183- CD194+ CD196+ /CXCR3- CCR4+ CCR6+ ), and CD4+ CD25++ blood T-cell phenotypes in 50 HEU and 25 HUU newborns. Early activation markers on CD4+ T cells and the Th cytokine profile produced from mononuclear cells under polyclonal T cell stimulation were also studied. Additionally, we probed the ability of CD4+ T cells to differentiate into interferon (IFN)-γ-producing Th1 CD4+ T cells in vitro. RESULTS: Lower percentages of differentiated Th1 , Th2 , Th17, and CD4+ CD25++ T cells were found in blood from HEU newborns than in blood from HUU newborns. However, polyclonally stimulated Th cells showed a similar ability to express CD69 and CD279 but produced less secreted interleukin (IL)-2 and IL-4. Interestingly, under Th1 differentiation conditions, the percentages of CD4+ IFN-γ+ T cells and soluble IFN-γ were higher in HEU newborns than in HUU newborns. CONCLUSION: HEU neonates are born with reduced proportions of differentiated Th1 /Th2 /Th17 and CD4+ CD25++ T cells, but the intrinsic abilities of CD4+ T cells to acquire a Th1 profile are not affected by the adverse maternal milieu during development.