Funding outcome

Infectious disease is a major cause of human infant mortality. According to a WHO estimate, almost 7 million children die each year before reaching their fifth birthday. Strikingly two-thirds of these deaths are due to infectious diseases. This has been attributed to the immaturity of the newborn immune system in the past. We recently discovered that immature red blood cells which are abundant in both mice and human during the neonatal period actively suppress their immune system. However, since newborns are colonized with a wide range of bacteria immediately after birth, immature red blood cells play a crucial role in early life for the gut to accept colonization with the good bacteria. As proof of concept, we found that following partial elimination of immature red blood cells, the gut immune cells became activated and cause inflammation. This shows that these cells prevent excessive inflammatory response to the microbial colonization in the gut in early exposure to the outside world. In agreement with this, our preliminary data show that immature red blood cells are present in the neonatal intestine and their depletion results in altered combination of the gut microbiome. Since altered microbiome in early life has been associated with autoimmune diseases and allergies in later life, I plan to understand how these immature red blood cells interact with the immune cells and also the gut microbiome. I will be working on the microbiome in the milk of mothers, fecal samples of newborns at 3 and 6 months of age and their mothers and correlate them with the percentages of immature red blood cells in the cord blood and placenta. In parallel, I also will use newborn animal models to characterise the role of immature red blood cells in adaptation of the newborns' gut to microbiome. Understanding the immune mechanisms that operate in infants is the key to developing new approaches to improve their health around the globe. Indeed, the challenges of infant infections and immune disorders may be two sides of the same phenomenon. As such, my studies will provide novel insight into mechanisms that govern the immunological differences seen in early life that result in extreme vulnerability to infections or cause autoimmune diseases later in life.