Immune development in HIV-exposed uninfected children born to HIV-infected women

Miyamoto, Maristela; Gouvêa, Aída F.T.B.; Ono, Érika; Succi, Regina C.M.; Pahwa, Savita; Moraes-Pinto, Maria Isabel de

doi:10.1590/s1678-9946201759030

Cited by 19 publications

(23 citation statements)

References 24 publications

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“…Recently, a study in Brazil compared plasma cytokine profiles and immunological cell subsets in HIV exposed and non HIV exposed children from birth to 6–12 years of age. At birth, no differences in cytokine levels, B cells, or MBC subsets (including atypical MBC) were found between the groups (90). Finally, pregnant women in Papua New Guinea with high malaria exposure also had elevated frequencies of atypical MBC, but cord blood MBC subset distribution was not examined (91).…”

Section: Discussionmentioning

confidence: 92%

HIV, Cytomegalovirus, and Malaria Infections during Pregnancy Lead to Inflammation and Shifts in Memory B Cell Subsets in Kenyan Neonates

Yeo

Embury

Anderson

et al. 2019

The Journal of Immunology

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Infections during pregnancy can expose the fetus to microbial antigens leading to inflammation that affects B cell development. Prenatal fetal immune priming may have an important role in infant acquisition of pathogen specific immunity. We examined plasma pro-inflammatory biomarkers, the proportions of various B cell subsets, and fetal priming to tetanus vaccination in cord blood from human US and Kenyan neonates. US neonates had no identified prenatal infectious exposures whereas Kenyan neonates examined had congenital CMV or mothers with prenatal HIV or Plasmodium falciparum, or no identified infectious exposures. Kenyan neonates had higher levels of IP-10, TNFα, CRP, sCD14 and BAFF than US neonates. Among the Kenyan groups, neonates with prenatal infections/infectious exposures had higher levels of cord blood INFɣ, IL-7, sTNFR1 and sTNFR2 compared to neonates with no infectious exposures. Kenyan neonates had greater proportions of activated memory B cells (MBC) compared to US neonates. Among the Kenyan groups, HIV exposed neonates had greater proportions of atypical MBC compared to the other groups. Although HIV exposed neonates had altered MBC subset distributions, detection of tetanus-specific MBC from cord blood, indicative of fetal priming with tetanus vaccine given to pregnant women, was comparable in HIV exposed and non HIV exposed neonates. These results indicate that the presence of infections during pregnancy induces fetal immune activation with inflammation and increased activated MBC frequencies in neonates. The immunologic significance and long term health consequences of these differences warrants further investigation.

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Section: Discussionmentioning

confidence: 92%

HIV, Cytomegalovirus, and Malaria Infections during Pregnancy Lead to Inflammation and Shifts in Memory B Cell Subsets in Kenyan Neonates

Yeo

Embury

Anderson

et al. 2019

The Journal of Immunology

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“…A previous study with HEU children from Brazil also revealed similar levels of microbial translocation and inflammation markers in plasma of HEU and unexposed children. 44 In HIV-infected individuals, alterations in gut microbiota are generally linked to increased microbial translocation. 18 Although we show that HEU children present differences in gut microbiota composition, there were no signs of microbial translocation, indicating that the microbiota alterations observed in HEU children are not directly linked to microbial translocation.…”

Section: Discussionmentioning

confidence: 99%

The impact ofin uteroHIV exposure on gut microbiota, inflammation, and microbial translocation

et al. 2019

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HIV-exposed but uninfected (HEU) children represent a growing population and show a significantly higher number of infectious diseases, several immune alterations, compromised growth, and increased mortality rates when compared to HIV-unexposed children. Considering the impact that the gut microbiota has on general host homeostasis and immune system development and modulation, we hypothesized that HEU children present altered gut microbiota that is linked to the increased morbidity and the immune system disorders faced by them. Our experiments revealed no differences in beta and alpha diversity of the gut microbiota between HEU and unexposed children or between HIV-infected and uninfected mothers. However, there were differences in the abundance of several taxa from the gut microbiota between HEU and unexposed children and between HIV-infected and uninfected mothers. Functional prediction based on 16S rRNA sequences also indicated differences between HEU and unexposed children and between infected and uninfected mothers. In addition, we detected no differences between HEU and unexposed children in relation to weight, weight-forage z scores, albumin serum levels, or microbial translocation and inflammation markers. In summary, HIV-infected mothers and their HIV-exposed children present alterations in the abundance of several taxa in the gut microbiome and the predicted functional metagenome when compared to uninfected mothers and unexposed children. Knowledge about the gut microbiome of HEU children in different settings is essential in order to determine better treatments for this susceptible population.

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“…The HIV-1-infected women selected for this sub-study were representative of the original HIV cohort as young, moderately immunosuppressed, without a medical history of HIV-related illnesses. Specifically, the median age at enrolment was 25 years (interquartile range (IQR), [23][24][25][26][27][28]. The women had a median CD4+ T cell count of 403 cells/ml (IQR, 313-523) and CD4:CD8 ratio of 0.44 (IQR, 0.29-0.73).…”

Section: Cohort Descriptionmentioning

confidence: 99%

“…The HIV uninfected motherinfant cohort was enrolled from a similar community. The median age at enrolment was 25 years (IQR, [23][24][25][26][27][28][29]. Infants born to HIV infected and HIV uninfected groups of women were of similar birth-weight: 3.3 kg (IQR, 3.0-3.6) vs 3.1 kg (IQR 2.9-3.5), respectively.…”

Section: Cohort Descriptionmentioning

confidence: 99%

“…Our studies focused on the prenatal cytokine environment in which presumably the cellular response would arise. In a study of plasma cytokines from HEU and HU infants born to HIV+ ARV-treated and healthy HIV− pregnant Brazilian women, HEU and HU cord blood plasma IL-8 levels were low and similar in HEU infants delivered via Caesarian section compared to HU infants delivered vaginally [28]. It remains an important public health goal to identify the effects of chronic maternal infections on fetal and infant immunity, correlations with infant health, and response to maternal antiviral treatments.…”

Section: Figmentioning

confidence: 99%

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HIV‐exposed uninfected infants: elevated cord blood Interleukin 8 (IL‐8) is significantly associated with maternal HIV infection and systemic IL‐8 in a Kenyan cohort

Lohman-Payne

Gabriel

Park

et al. 2018

Clinical & Translational Med

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Background In low and middle income countries, human immunodeficiency virus (HIV) exposed, uninfected (HEU) infants demonstrate higher morbidity and mortality than their unexposed counterparts. To determine possible immune correlates of this effect, we investigated the impact of in utero HIV exposure on the uninfected neonatal immune milieu and maternal factors mediating these abnormalities in a cohort of vaginally delivered mother-infants. Samples of delivery and cord blood plasma were selected from 22 Kenyan HIV-infected women and their HIV exposed uninfected (HEU) infants drawn from the pre-ARV era, while 19 Kenyan HIV-uninfected (HU) women and their infants were selected from a control cohort. Results Compared to HU cord plasma, HEU cord plasma contained significantly higher levels of pro-inflammatory cytokines interleukins (IL)-6 and -8 (both p < 0.001) and significantly lower levels of CXC motif chemokine 11 (CXC11) (p < 0.001). Mediation analysis demonstrated that maternal HIV infection status was a significant determinant of infant IL-8 responses: HEU status was associated with a ninefold higher infant:mother (cord:delivery) plasma levels of IL-8 (p < 0.005), whereas maternal viral load was negatively associated with HEU IL-8 levels (p = 0.04) and not associated with HEU IL-6 levels. Conclusions Exposure to maternal HIV infection drives an increase in prenatal IL-8 that is partially mediated by maternal cytokine levels. Differences between maternal and infant cytokine levels strongly suggest independent modulation in utero, consistent with prenatal immune activation. Elevated pro-inflammatory signals at birth may interfere with T cell responses at birth and subsequently influence immune maturation and the risk of morbidity and mortality in HEU infants.

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Immune development in HIV-exposed uninfected children born to HIV-infected women

Cited by 19 publications

References 24 publications

HIV, Cytomegalovirus, and Malaria Infections during Pregnancy Lead to Inflammation and Shifts in Memory B Cell Subsets in Kenyan Neonates

HIV, Cytomegalovirus, and Malaria Infections during Pregnancy Lead to Inflammation and Shifts in Memory B Cell Subsets in Kenyan Neonates

The impact ofin uteroHIV exposure on gut microbiota, inflammation, and microbial translocation

HIV‐exposed uninfected infants: elevated cord blood Interleukin 8 (IL‐8) is significantly associated with maternal HIV infection and systemic IL‐8 in a Kenyan cohort

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