Bovine immune responses to pathogen transmission
One of the most important diseases in cattle worldwide is bovine anaplasmosis, caused by the intracellular bacterium Anaplasma marginale. The pathogen is transmitted by several tick species. This means that ticks acquire the pathogen from an infected animal, harbor it, and pass it on to uninfected cattle during the feeding process. This disease currently represents a huge burden on the cattle industry because of the cost of cattle treatment and monetary losses that are sustained as a result of the infection.
To address this issue, the Chavez lab will be conducting a large research project. The goal of our project is to better understand, on a molecular level, what is happening at the interface between the tick, the pathogen, and the skin of the cattle being fed on by a tick harboring Anaplasma marginale. A complete understanding of the tick-pathogen-host interaction, beginning at the inception of the infection, has remained elusive to science. By characterizing these processes, we will answer some very important scientific questions pertinent to solving the problems that are caused by this disease. Two broad questions we will answer are, how does this pathogen establish an infection?
What molecular components are responsible for allowing A. marginale to evade the host immune system? Understanding this process may, one day, lay the framework for developing an effective vaccine against A. marginale in cows.
Our study will be tasked with characterizing the immune response that occurs at the tick feeding site during pathogen transmission. Also, defining what pathways are hijacked by A. marginale to manipulate tick salivary secretions will be a key aspect of our project. Finally, we will identify and describe bacterial virulence factors that are secreted within the tick saliva. This project will lay more groundwork for future studies into the interface between tick-pathogen-host systems. There are many diseases transmitted by many species of ticks to many different mammalian hosts. Understanding the processes described above is paramount for fighting against the debilitating diseases caused by deadly pathogens. We aim to fight back against these pathogens through the use of good science.
Investigating Co-transmission of A. phagocytophilum and B. burgdoferi from the deer tick I. scapularis
Ticks harbor and transmit pathogens that cause many debilitating diseases. The number of infections that result from tick feeding on humans is expected to increase in coming years due to growing tick populations. A large concern stemming from the increasing occurrence of tick-borne illness is the ability of ticks to transit more than one pathogen at a time. This phenomenon is deemed co-infection. The deer tick, Ixodes scapularis, can be co-infected with up to 7 different pathogens, which could potentially be transmitted to humans. This is alarming due to the incomplete understanding of how co-infection may affect disease progression, including the synergistic effects individual pathogens exhibit on each other during co-transmission.
Currently, the most prevalent co-infection in ticks and humans involves simultaneous infection with Borrelia burgdorferi and Anaplasma phagocytophilum, the causative agent of Lyme Disease and Human Granulocytic Anaplasmosis (HGA), respectively. The causative agents of Lyme Disease and HGA have evolved mechanisms to alter host immune responses to establish infection. Given that the skin is the first site of infection for tick-borne pathogens, it is of interest to address how the localized skin immune response affects this process. This project will identify which virulence factors are at play, and identify what mechanisms these effectors use to alter immune function.
Immune cell populations are also likely affected during disease transmission. Our project will also identify how the immune response is altered by identifying changes to the immune cell population during transmission. Finally, we will identify the changes in signalling molecules that orchestrate the engagement of specific cell populations at the skin during transmission and co-transmission. Using innovative approaches, we aim to unravel bacterial virulence factors that influence immune cell populations and signaling pathways in the skin. The results from these studies will serve as the foundation for future studies looking at the mechanisms that these bacteria use to modify tick salivary components and alter the localized skin immune response. This information can then be utilized in the development of effective vaccines and for preventive strategies against pathogen establishment.