Decoding viral transmission, tropism and inflammation: from single cell to organism

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

Inflammation is activation of the immune system. It plays an important role for fighting infectious pathogens but unregulated contributes to the development of many childhood and adult chronic diseases including cardiovascular disease, arthritis, diabetes, Parkinsons, multiple sclerosis and Alzheimers. Our lab studies the external and internal triggers and regulators of inflammation in the body. Viruses going into cells can trigger inflammation. We discovered that viruses must enter cells in supraunitary numbers in order to replicate and not trigger inflammation. One line of investigation we pursue is to identify the cellular components responsible for mounting/ not-mounting inflammatory responses against viruses. The levels of these components we believe vary across cells in the body and determine the overall inflammatory state of those cells and whether viruses entering them can replicate or not. We have developed a methodology- combining computational and experimental tools- to identify cells where inflammation pathways are activated. Our lab is also focused on the role of breastfeeding in protecting children from infections and inflammatory diseases such as asthma. Indeed, children who are breastfed have lower incidence of obesity, diabetes, asthma, sudden infant death syndrome, otitis media, lower respiratory tract illnesses, and gastrointestinal infections. Our studies are finding that breastmilk composition ( antibodies, immune cells, metabolites) is highly dynamic and attunes rapidly to the health state of the infant that is breastfeeding. Furthermore antibodies and immune cells shed in breastmilk we find are transmitted to the child and incorporate into the childs tissues, helping shape the child immune landscape and determine future susceptibility of their immune system to abnormal inflammation. Inflammation is a critical basis of many childhood and adult chronic diseases including cardiovascular disease, diabetes, arthritis, Parkinson and Alzheimers. We are using both animal model systems and clinical human samples. Animal model systems recapitulate the breastfeeding mother-infant human model. The human breastmilk samples are collected/donated and used to verify the findings in animal models. A significant number of individuals who have been infected with SARS-COV2 develop chronic conditions including cardiovascular disease, kidney function problems, neurological problems. The common factor connecting these seemingly disparate conditions is again inflammation. Our studies investigating the coronavirus cellular exit pathways have revealed that these viruses disrupt antigen presentation pathways in the cells and this leads to activation of natural killer cells of the body leading to aberrant inflammation. Finally salivary glands are the gateway to the GI tract , produce saliva which contains digestive enzymes, antibodies and anti-microbial metabolites. Disruption of normal salivary gland functions leads to susceptibility to food based allergens, pathogens, and long term GI problems. Our lab is dissecting the immunobiology of the salivary gland which is critical for normal salivary functions. We have discovered a new immune cell type in the salivary glands that regulates inflammation and autoimmunity.