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

Abstract

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.

A longitudinal study of plasma BAFF levels in mothers and their infants in Uganda, and correlations with subsets of B cells

“…In our relatively large cohort of newborns and their mothers, mean BAFF-levels in cord blood were 2075 pg/mL and in mothers 670 pg/mL. These results are in the same order as those found both in malaria-free areas and in Kenya [ 34 , 35 , 37 ]. Mesenchymal cells in term placental villi are major sites of BAFF synthesis [ 28 ] which may explain the substantially higher levels of BAFF seen in newborns compared to their mothers.…”

“…Previous studies investigating BAFF concentrations in infants and mothers have been conducted both in non-endemic countries in Europe [ 33 – 35 ], and in Kenya [ 37 ]. Consistent with these publications, our results show overall higher levels of BAFF in infants than in mothers, possibly mirroring a developing immune system.…”

“…The levels of BAFF in newborns from malaria-endemic areas is of interest given the potential in utero exposure to an infection skewing the B cell response. A recently published study in Kenya showed that levels of BAFF in cord blood of healthy newborns were double that of their mothers’ levels at birth [ 37 ]. In the current study, we sought to measure the plasma BAFF-levels in mothers and their infants in a malaria-endemic setting.…”

Epidemiology of Cytomegalovirus among pregnant women in Africa

“…This immune environment facilitates inflammation and viral replication in host cells, hence increasing chances of viral shedding into the mucosa and body fluids. CMV has been described as a disease of inflammation in pregnancy [92], but the dynamics of immune activation, CMV DNAemia and CMV acquisition/transmission are unknown. In the study carried out among Kenyan HIV-infected infants, mentioned earlier in this review, the CMV-induced increase in T-cell activation and apoptosis observed could potentially be a marker of CMV-induced immune activation [51].…”

Mediterranean Diet: Lipids, Inflammation, and Malaria Infection

“…Infections during pregnancy might expose the fetus to microbial antigens triggering inflammation and fetal immune response, affecting the B cell. It could prime the infant immune system and its response against a challenge might be augmented [ 82 ]. Ly and Hansen reviewed the importance of a proper response and the generation of a long-term B cell memory in malaria infection [ 83 ].…”