Abstract The importance of fetal placental macrophages (Hofbauer cell [HCs]) is underscored by their appearance 18 d postconception and maintenance through term; however, how human HCs evolve during healthy pregnancy and how microenvironment and ontogeny impact phenotype and function remain unknown. In this study, we comprehensively classify human HCs ex vivo, interrogate phenotypic plasticity, and characterize antiviral immune responses through gestation. Activated HCs were abundant in early pregnancy and decreased by term; molecular signatures emphasize inflammatory phenotypes early in gestation. Frequency of HCs with regulatory phenotypes remained high through term. Furthermore, term HCs exhibited blunted responses to stimulation, indicating reduced plasticity. IFN-λ1 is a key placental IFN that appeared less protective than IFN-α, suggesting a potential weakness in antiviral immunity. Ligand-specific responses were temporally regulated: we noted an absence of inflammatory mediators and reduced antiviral gene transcription following RIG-I activation at term despite all HCs producing inflammatory mediators following IFN-γ plus LPS stimulation. Collectively, we demonstrate sequential, evolving immunity as part of the natural history of HCs through gestation.
A Multicenter Analysis of Elvitegravir Use During Pregnancy on HIV Viral Suppression and Perinatal Outcomes
OBJECTIVES: We compared demographics and work, financial, and satisfaction experiences of early-career and midcareer pediatricians categorized by their childhood and medical school locations. METHODS: Data from the Pediatrician Life and Career Experience Study were used to examine the characteristics and experiences of 3 groups, which were categorized as (1) international childhood and medical school graduate (international-IMG), (2) United States childhood and international medical school graduate (US-IMG), and (3) United States or international childhood and United States medical school graduate (USMG). With multivariable logistic regression, we examined the experiences of the groups, controlling for participant characteristics. RESULTS: Data from 1467 of 1804 participants were analyzed; 13% were categorized as international-IMGs, 6% were categorized as US-IMGs, and 81% were categorized as USMGs. International-IMGs and US-IMGs were less likely than USMGs to report their race and ethnicity as white and non-Hispanic (26%, 32%, and 71%, respectively; P < .05) and more likely to report caring for patients with public insurance (adjusted odds ratio [aOR] 1.80 [95% confidence interval (CI) 1.27–2.56] and aOR 2.12 [95% CI 1.31–3.42], respectively). International-IMGs were less likely than USMGs to agree that physician colleagues value their work (aOR 0.35; 95% CI 0.21–0.56). Overall, 8 in 10 reported that their work was personally rewarding; international-IMGs were less likely than USMGs to report such satisfaction (P < .05). CONCLUSIONS: Among a national sample of pediatricians, international-IMGs and US-IMGs play important roles in workforce diversity. They also report unique challenges. Most are satisfied with their work, but international-IMGs are the least satisfied.