Biology subjects

Milburn, L.

Publications and source records attributed to Milburn, L..

2 recordsLinked to original sources

bioRxiv2024

Breastmilk IgG engages the neonatal immune system to instruct host-microbiota mutualism

Maternal antibodies fundamentally regulate infant immunity to the developing gut microbiota, yet the mechanisms underlying this process remain elusive. Here, we show that maternal IgG, ingested in the first week of life, functions to restrain microbiota-dependent adaptive immune responses and reduce offspring susceptibility to intestinal inflammation weeks later, following weaning. To exert these functions, efficient binding of IgG to gut bacterial antigens and engagement of Fc and complement dependent effector functions in offspring was required. These discoveries reveal a novel mechanism wherein maternal IgG engages the offspring immune system to calibrate responses to gut microbes. This mode of maternal immune instruction may provide adaptability to developmental shifts in microbiota necessary for establishing host-microbiota mutualism and limiting susceptibility to inflammatory disease. One sentence abstractIngestion of maternal IgG during a discrete postnatal window calibrates neonatal immunity to the gut microbiota.

immunology↗

bioRxiv2021

Nuclear Hormone Receptor NHR-49 controls a HIF-1-independent hypoxia adaptation pathway in Caenorhabditis elegans

The response to insufficient oxygen (hypoxia) is orchestrated by the conserved Hypoxia-Inducible Factor (HIF). However, HIF-independent hypoxia response pathways exist that act in parallel to HIF to mediate the physiological hypoxia response. Here, we describe a HIF-independent hypoxia response pathway controlled by Caenorhabditis elegans Nuclear Hormone Receptor NHR-49, an orthologue of mammalian Peroxisome Proliferator-Activated Receptor alpha (PPAR). We show that nhr-49 is required for worm survival in hypoxia and is synthetic lethal with hif-1 in this context, demonstrating that these factors act independently. RNA-seq analysis shows that in hypoxia nhr-49 regulates a set of genes that are hif-1-independent, including autophagy genes that promote hypoxia survival. We further show that Nuclear Hormone Receptor nhr-67 is a negative regulator and Homeodomain-interacting Protein Kinase hpk-1 is a positive regulator of the NHR-49 pathway. Together, our experiments define a new, essential hypoxia response pathway that acts in parallel to the well-known HIF-mediated hypoxia response.

genetics↗