Maternal IgE activates fetal mast cells: Mast cells (MCs) are immune cells that participate in allergic reactions through their activation by immunoglobulin E (IgE) antibodies. MCs arise early during mammalian development, but it is unclear whether IgE-mediated activation occurs in fetal tissues and what the source of IgE stimulation is. Msallam et al. show that human and mouse fetal MCs can be sensitized by IgE of maternal origin, which crosses the placental barrier through the fetal neonatal Fc receptor (see the Perspective by Rothenberg). Prenatal maternal sensitization conferred transient allergen sensitivity after birth and resulted in the development of postnatal skin and airway inflammation in the offspring after their first exposure to allergen. Thus, both maternal IgE and fetal MCs may influence mother-to-child transmission of allergic disease during gestation. Science , this issue p. 941 ; see also p. 907

Infection of fetuses with Zika virus during pregnancy and congenital defects are enhanced by maternal immunity to dengue virus.

Sequential exposures to flaviviruses sharing CD4 epitopes promote protection during subsequent heterologous infections.

Mosquito blood-feeding behavior is a key determinant of the epidemiology of dengue viruses (DENV), the most-prevalent mosquito-borne viruses. However, despite its importance, how DENV infection influences mosquito blood-feeding and, consequently, transmission remains unclear. Here, we developed a high-resolution, video-based assay to observe the blood-feeding behavior of Aedes aegypti mosquitoes on mice. We then applied multivariate analysis on the high-throughput, unbiased data generated from the assay to ordinate behavioral parameters into complex behaviors. We showed that DENV infection increases mosquito attraction to the host and hinders its biting efficiency, the latter resulting in the infected mosquitoes biting more to reach similar blood repletion as uninfected mosquitoes. To examine how increased biting influences DENV transmission to the host, we established an in vivo transmission model with immuno-competent mice and demonstrated that successive short probes result in multiple transmissions. Finally, to determine how DENV-induced alterations of host-seeking and biting behaviors influence dengue epidemiology, we integrated the behavioral data within a mathematical model. We calculated that the number of infected hosts per infected mosquito, as determined by the reproduction rate, tripled when mosquito behavior was influenced by DENV infection. Taken together, this multidisciplinary study details how DENV infection modulates mosquito blood-feeding behavior to increase vector capacity, proportionally aggravating DENV epidemiology. By elucidating the contribution of mosquito behavioral alterations on DENV transmission to the host, these results will inform epidemiological modeling to tailor improved interventions against dengue. Significance Because dengue viruses are spread by mosquitoes during biting, transmission capacity depends on mosquito-biting behavior. For this reason, it is critical to understand how infection in mosquitoes influences biting. To answer this question, we deployed a multidisciplinary approach including high-resolution, multivariate biting behavior monitoring on mice, in vivo transmission assay, and mathematical modeling. We demonstrated that infected mosquitoes are more attracted to mice and bite more often to get the same amount of blood as uninfected mosquitoes. While the effect of increased attraction to host on transmission capacity is trivial, we showed that increased number of bites results in successive transmission. Eventually, we calculated that the infection-induced behavior changes tripled transmission capacity of mosquitoes.

Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in severely ill patients and the pathophysiology of disease is thought to be immune-mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens, often promoting inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and non-human primates. Using a mouse model of MC-deficiency, MC-dependent interstitial pneumonitis, hemorrhaging, and edema in the lung were observed during SARS-CoV-2 infection. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype in severe disease. MC activation in humans was confirmed, through detection of MC-specific proteases, including chymase, levels of which were significantly correlated with disease severity and with biomarkers of vascular dysregulation. These results support the involvement of MCs in lung tissue damage during SARS-CoV-2 infection in animal models and the association of MC activation with severe COVID-19 in humans, suggesting potential strategies for intervention.