Analysis of the Peripheral Blood Transcriptome to Identify Clinical Correlates of Pathology in Patients with Babesiosis
Abstract
Rationale Babesiosis is a tick-borne disease that is caused by parasites that infect red blood cells. Very young age, advanced age, or immune suppression predispose people to severe and even life-threatening disease. However, the reason some individuals develop severe disease and others have no symptoms is largely unknown. In fact, severe disease is sometimes independent of how many parasites are present in the person. The goal of this proposal is to use new scientific advances to globally examine how the parasite and the human impact one another during human babesiosis. This knowledge will enable us to identify how differences in immune responses and/or the parasite can affect whether someone develops severe babesiosis. Scientific Objective The goal of the proposal is to identify parasite and immune factors that impact one another during human babesiosis. It is currently not known what constitutes an effective immune response versus a pathological response that could lead to life-threatening complications. This is a crucial gap that impacts our ability to treat babesiosis and to identify complications before they become life threatening. Our goal is to understand how the parasite and immune response impact disease severity so that we can intervene with the most effective treatment and so that physicians can predict complications before they become life threatening. Relevance The proposal is directly relevant to (1) Pathogenesis: Understanding the Immunological Mechanisms of Immune Protection for Lyme Disease or Other Tick-Borne Diseases. Specific Aim 1 Identify host and parasite mediators associated with parasite replication versus killing of parasites during infection. We will use a mouse model of babesiosis that has distinct phases in which the parasite is clearly increasing in numbers early in infection and is killed late in infection. This will allow us to determine parasite and host pathways that seem to be important for a permissive infection versus those important for killing of the parasites and ultimately, a positive outcome to infection. This is important, as host and parasite pathways that are important for controlling disease versus those for severe disease are largely unknown. We will take what we learn about parasite and host factors important for eliminating disease versus severe outcomes of infection in Aim 1 to help us understand what happens during human babesiosis. Specific Aim 2 Identify parasite and host signatures of human babesiosis, including correlates of disease severity. The goal is to understand the important differences in the infecting parasite and the person infected that result in severe disease versus relatively mild disease. Innovation Our studies are highly innovative. They will apply state-of-the-art scientific advances in tools to analyze the genes that are expressed during infection and how their changes in expression impact human babesiosis. This has never been done before. We also take the highly innovative approach of evaluating the whole peripheral blood environment, including different types of RNA to examine host and pathogen effects on one another during human disease, as well as systemic effects that may contribute to diverse complications of babesiosis. To ensure the translation of discovery to clinical application, we include comprehensive descriptions of clinical pathophysiological features of human babesiosis. The goal is to link pathological mechanisms of disease to changes in gene expression in both the parasite and the peripheral blood environment. Ultimate Applicability of the Research The proposed studies will be a revolutionary step forward for our understanding of human babesiosis, in part because so little is currently known. Candidate host and parasite factors that we discover are associated with human disease and potentially disease severity, will be validated and their importance in disease progression will be evaluated in murine
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010508
Entities
People
- Dana Mordue
Organizations
- New York Medical College
- United States Army