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1.
Am J Physiol Regul Integr Comp Physiol ; 322(2): R99-R111, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1630162

ABSTRACT

A prominent health issue nowadays is the COVID-19 pandemic, which poses acute risks to human health. However, the long-term health consequences are largely unknown and cannot be neglected. An especially vulnerable period for infection is pregnancy, when infections could have long-term health effect on the child. Evidence suggests that maternal immune activation (MIA) induced by either bacteria or viruses presents various effects on the offspring, leading to adverse phenotypes in many organ systems. This review compares the mechanisms of bacterial and viral MIA and the possible long-term outcomes for the offspring by summarizing the outcome in animal LPS and Poly I:C models. Both models are activated immune responses mediated by Toll-like receptors. The outcomes for MIA offspring include neurodevelopment, immune response, circulation, metabolism, and reproduction. Some of these changes continue to exist until later life. Besides different doses and batches of LPS and Poly I:C, the injection day, administration route, and also different animal species influence the outcomes. Here, we specifically aim to support colleagues when choosing their animal models for future studies.


Subject(s)
COVID-19/complications , COVID-19/immunology , Lipopolysaccharides/toxicity , Poly I-C/toxicity , Prenatal Exposure Delayed Effects/immunology , SARS-CoV-2 , Bacterial Infections/immunology , Female , Humans , Pregnancy
2.
Cells ; 10(12)2021 12 11.
Article in English | MEDLINE | ID: covidwho-1598389

ABSTRACT

Both in utero exposure to maternal immune activation and cannabis use during adolescence have been associated with increased risk for the development of schizophrenia; however, whether these exposures exert synergistic effects on brain function is not known. In the present study, mild maternal immune activation (MIA) was elicited in mice with prenatal exposure to polyinosinic-polycytidylic acid (poly(I:C)), and ∆9-tetrahydrocannabinol (THC) was provided throughout adolescence in cereal (3 mg/kg/day for 5 days). Neither THC nor MIA pretreatments altered activity in assays used to characterize hyperdopaminergic states in adulthood: amphetamine hyperlocomotion and prepulse inhibition of the acoustic startle reflex. Adolescent THC treatment elicited deficits in spatial memory and enhanced spatial reversal learning in adult female mice in the Morris water maze, while exposure to MIA elicited female-specific deficits in fear extinction learning in adulthood. There were no effects in these assays in adult males, nor were there interactions between THC and MIA in adult females. While doses of poly(I:C) and THC were sufficient to elicit behavioral effects, particularly relating to cognitive performance in females, there was no evidence that adolescent THC exposure synergized with the risk imposed by MIA to worsen behavioral outcomes in adult mice of either sex.


Subject(s)
Aging/physiology , Behavior, Animal/drug effects , Dronabinol/pharmacology , Prenatal Exposure Delayed Effects/immunology , Amphetamine , Animals , Conditioning, Classical , Extinction, Psychological/drug effects , Fear/drug effects , Female , Locomotion/drug effects , Male , Maze Learning/physiology , Mice, Inbred C57BL , Pregnancy , Prepulse Inhibition/drug effects , Rats, Sprague-Dawley , Reflex, Startle/drug effects , Swimming
3.
Am J Physiol Regul Integr Comp Physiol ; 322(2): R99-R111, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1555140

ABSTRACT

A prominent health issue nowadays is the COVID-19 pandemic, which poses acute risks to human health. However, the long-term health consequences are largely unknown and cannot be neglected. An especially vulnerable period for infection is pregnancy, when infections could have long-term health effect on the child. Evidence suggests that maternal immune activation (MIA) induced by either bacteria or viruses presents various effects on the offspring, leading to adverse phenotypes in many organ systems. This review compares the mechanisms of bacterial and viral MIA and the possible long-term outcomes for the offspring by summarizing the outcome in animal LPS and Poly I:C models. Both models are activated immune responses mediated by Toll-like receptors. The outcomes for MIA offspring include neurodevelopment, immune response, circulation, metabolism, and reproduction. Some of these changes continue to exist until later life. Besides different doses and batches of LPS and Poly I:C, the injection day, administration route, and also different animal species influence the outcomes. Here, we specifically aim to support colleagues when choosing their animal models for future studies.


Subject(s)
COVID-19/complications , COVID-19/immunology , Lipopolysaccharides/toxicity , Poly I-C/toxicity , Prenatal Exposure Delayed Effects/immunology , SARS-CoV-2 , Bacterial Infections/immunology , Female , Humans , Pregnancy
5.
Neuropharmacology ; 201: 108841, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1466809

ABSTRACT

A strong association between perinatal viral infections and neurodevelopmental disorders has been established. Both the direct contact of the virus with the developing brain and the strong maternal immune response originated by viral infections can impair proper neurodevelopment. Coronavirus disease 2019 (COVID-19), caused by the highly-infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently responsible for a large global outbreak and is a major public health issue. While initial studies focused on the viral impact on the respiratory system, increasing evidence suggest that SARS-CoV-2 infects other organs and tissues including the mature brain. While studies continue to determine the neuropathology associated to COVID-19, the consequences of SARS-CoV-2 infection to the developing brain remain largely unexplored. The present review discusses evidence suggesting that SARS-CoV-2 infection may have persistent effects on the course of pregnancy and on brain development. Studies have shown that several proinflammatory mediators which are increased in the SARS-CoV-2-associated cytokine storm, are also modified in other viral infections known to increase the risk of neurodevelopmental disorders. In this sense, further studies should assess the genuine effects of SARS-CoV-2 infection during pregnancy and delivery along with an extended follow-up of the offspring, including neurocognitive, neuroimaging, and electrophysiological examination. It also remains to be determined whether and by which mechanisms SARS-CoV-2 intrauterine and early life infection could lead to an increased risk of developing neuropsychiatric disorders, such as autism (ASD) and schizophrenia (SZ), in the offspring.


Subject(s)
Autism Spectrum Disorder/epidemiology , COVID-19/epidemiology , Cytokine Release Syndrome/epidemiology , Neurodevelopmental Disorders/epidemiology , Pregnancy Complications, Infectious/epidemiology , Prenatal Exposure Delayed Effects/epidemiology , Schizophrenia/epidemiology , Autism Spectrum Disorder/immunology , Brain/embryology , Brain/immunology , COVID-19/immunology , Cytokine Release Syndrome/immunology , Female , Humans , Infectious Disease Transmission, Vertical , Neurodevelopmental Disorders/immunology , Pregnancy , Pregnancy Complications, Infectious/immunology , Prenatal Exposure Delayed Effects/immunology , Risk Factors , SARS-CoV-2 , Schizophrenia/immunology
6.
J Allergy Clin Immunol ; 148(3): 843-857.e6, 2021 09.
Article in English | MEDLINE | ID: covidwho-1213300

ABSTRACT

BACKGROUND: Prenatal exposure to infections can modify immune development. These environmental disturbances during early life potentially alter the incidence of inflammatory disorders as well as priming of immune responses. Infection with the helminth Schistosoma mansoni is widely studied for its ability to alter immune responsiveness and is associated with variations in coinfection, allergy, and vaccine efficacy in endemic populations. OBJECTIVE: Exposure to maternal schistosomiasis during early life, even without transmission of infection, can result in priming effects on offspring immune responses to bystander antigenic challenges as related to allergic responsiveness and vaccination, with this article seeking to further clarify the effects and underlying immunologic imprinting. METHODS: Here, we have combined a model of chronic maternal schistosomiasis infection with a thorough analysis of subsequent offspring immune responses to allergy and vaccination models, including viral challenge and steady-state changes to immune cell compartments. RESULTS: We have demonstrated that maternal schistosomiasis alters CD4+ responses during allergic sensitization and challenge in a skewed IL-4/B-cell-dominant response to antigenic challenge associated with limited inflammatory response. Beyond that, we have uncovered previously unidentified alterations to CD8+ T-cell responses during immunization that are dependent on vaccine formulation and have functional impact on the efficacy of vaccination against viral infection in a murine hepatitis B virus model. CONCLUSION: In addition to steady-state modifications to CD4+ T-cell polarization and B-cell priming, we have traced these modified CD8+ responses to an altered dendritic cell phenotype sustained into adulthood, providing evidence for complex priming effects imparted by infection via fetomaternal cross talk.


Subject(s)
Prenatal Exposure Delayed Effects/immunology , Respiratory Hypersensitivity/immunology , Schistosomiasis/immunology , Allergens/immunology , Animals , B-Lymphocytes/immunology , Cells, Cultured , Dendritic Cells/immunology , Female , Fetus/immunology , Gene Expression Profiling , Immunization , Lung/immunology , Lymph Nodes/immunology , Male , Mice, Inbred BALB C , Mice, Inbred C57BL , Ovalbumin/immunology , Pregnancy , Respiratory Hypersensitivity/genetics , Schistosoma mansoni , Spleen/immunology , T-Lymphocytes/immunology
7.
Am J Reprod Immunol ; 84(5): e13306, 2020 11.
Article in English | MEDLINE | ID: covidwho-708944

ABSTRACT

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 12 million infections and more than 550 000 deaths.1 Morbidity and mortality appear partly due to host inflammatory response.2 Despite rapid, global research, the effect of SARS-CoV-2 on the developing fetus remains unclear. Case reports indicate that vertical transmission is uncommon; however, there is evidence that placental and fetal infection can occur.3-7 Placentas from infected patients show inflammatory, thrombotic, and vascular changes that have been found in other inflammatory conditions.8,9 This suggests that the inflammatory nature of SARS-CoV-2 infection during pregnancy could cause adverse obstetric and neonatal events. Exposure to intrauterine inflammation and placental changes could also potentially result in long-term, multisystemic defects in exposed infants. This review will summarize the known literature on the placenta in SARS-CoV-2 infection, evidence of vertical transmission, and possible outcomes of prenatal exposure to the virus.


Subject(s)
COVID-19/immunology , Placenta/immunology , Pregnancy Complications, Infectious/immunology , Pregnancy , Prenatal Exposure Delayed Effects/immunology , SARS-CoV-2/physiology , COVID-19/transmission , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Pandemics , Placenta/virology
9.
J Allergy Clin Immunol ; 146(1): 101-109.e1, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-619994

ABSTRACT

BACKGROUND: Immunologic dysfunction due to coronavirus disease 2019 (COVID-19) is closely related to clinical prognosis, and the inflammatory response of pregnant women may affect the directional differentiation and function of fetal immune cells. OBJECTIVE: We sought to analyze the immune status of newborns from mothers with COVID-19 in the third trimester. METHODS: Along with collecting the clinical data from 51 newborns and their respective mothers, we recorded the immunophenotypes and cytokine and immunoglobulin levels of the newborns. RESULTS: None of the 51 newborns showed fever or respiratory distress during hospitalization. Detection of severe acute respiratory syndrome coronavirus 2 nucleic acid in pharyngeal swabs was negative. Except for the low level of CD16-CD56 cells, the count and proportion of lymphocytes, CD3, CD4, CD8, and CD19 were all in the normal range. Moreover, the serum IgG and IgM levels were within the normal range, whereas IL-6 showed increased levels. There was no correlation between maternal COVID-19 duration and the lymphocyte subsets or cytokine levels (IFN-γ, IL-2, IL-4, IL-6, IL-10, and TNF-α). There was a positive correlation between IL-6 and IL-10 levels and CD16-CD56 cells. One (1.96%) infant with an extremely elevated IL-6 concentration developed necrotizing enterocolitis in the third week after birth, and the remaining 50 infants did not show abnormal symptoms through the end of the follow-up period. CONCLUSIONS: COVID-19 in the third trimester did not significantly affect the cellular and humoral immunity of the fetus, and there was no evidence that the differentiation of lymphocyte subsets was seriously unbalanced.


Subject(s)
Coronavirus Infections/immunology , Infant, Newborn/immunology , Pneumonia, Viral/immunology , Pregnancy Complications, Infectious/immunology , Prenatal Exposure Delayed Effects/immunology , Betacoronavirus , COVID-19 , China , Female , Humans , Lymphocyte Subsets/immunology , Male , Pandemics , Pregnancy , Pregnancy Trimester, Third , SARS-CoV-2
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