MDA5 signaling induces type 1 IFN- and IL-1-dependent lung vascular permeability which protects mice from opportunistic fungal infection.

Lungs balance threat from primary viral infection, secondary infection, and inflammatory damage. Severe pulmonary inflammation induces vascular permeability, edema, and organ dysfunction. We previously demonstrated that poly(I:C) (pICLC) induced type 1 interferon (t1IFN) protected mice from Cryptococcus gattii (Cg) via local iron restriction. Here we show pICLC increased serum protein and intravenously injected FITC-dextran in the lung airspace suggesting pICLC induces vascular permeability. Interestingly, pICLC induced a pro-inflammatory signature with significant expression of IL-1 and IL-6 which depended on MDA5 and t1IFN. Vascular permeability depended on MDA5, t1IFN, IL-1, and IL-6. T1IFN also induced MDA5 and other MDA5 signaling components suggesting that positive feedback contributes to t1IFN dependent expression of the pro-inflammatory signature. Vascular permeability, induced by pICLC or another compound, inhibited Cg by limiting iron. These data suggest that pICLC induces t1IFN which potentiates pICLC-MDA5 signaling increasing IL-1 and IL-6 resulting in leakage of antimicrobial serum factors into lung airspace. Thus, induced vascular permeability may act as an innate defense mechanism against opportunistic fungal infection, such as cryptococcosis, and may be exploited as a host-directed therapeutic target.

Human milk-sharing practices and infant-feeding behaviours: A comparison of donors and recipients.

Human milk sharing (HMS) is growing in popularity as an infant-feeding strategy in the United States. HMS families are a hidden population because HMS is a nonnormative and stigmatized behaviour. Thus, gaining access to HMS participants is challenging, and research on this topic remains limited. In particular, little is known about the broader infant-feeding behaviours of HMS parents. This study aimed to describe and compare the infant-feeding behaviours and HMS practices among a network of HMS donors and recipients. A detailed online survey was distributed to HMS parents in the Washington, DC region. Bivariate analyses were used to summarize the data by donor/recipient status when possible. Group differences were tested using analysis of variance for continuous variables and χ2 tests for categorical variables. Donors and recipients did not differ in their sociodemographic characteristics. Recipients were significantly more likely than donors to have experienced complications of labour and delivery, traumatic birth, postpartum depression or a negative breastfeeding experience. Donors and recipients did not differ significantly in their duration of lactation or HM-feeding. Interestingly, 30% of recipients ever produced excess milk and 21% of donors ever had difficulty producing enough milk for their child. Compared with donors, recipients faced numerous maternal health challenges, but were still able to achieve a long duration of HM-feeding. HMS recipients represent a vulnerable group who may benefit from additional psychosocial and lactation support to improve their health and breastfeeding outcomes. Additional research is needed to investigate the associations between HMS participation, infant-feeding behaviours and lactation outcomes.