Summary. Lyme Disease cases have increased more than 200% in the last decade. Antibiotic therapy is
often effective, though many patients experience long-lasting complications, and it is not yet known why some
patients develop chronic arthritis and neurologic involvement. Borrelia burgdorferi senso lato, the agent that
causes Lyme Disease, is carried by the tick vector Ixodes scapularis. In addition to transmitting Lyme Disease
I. scapularis carries and transmits other microorganisms, including species of Ehrlichia, Babesia, Anaplasma,
as well as viral pathogens. This is significant as patients with tick-borne co-infections often exhibit more
severe symptoms. It is currently unclear how the host innate immune system handles multiple pathogen types
simultaneously. We propose to examine the impact of early innate myeloid cells on control of B. burgdorferi in
mice co-infected with pathogens that are also transmitted by I. scapularis. Based on preliminary data we
hypothesize that co-infecting pathogens elicit myeloid responses that are not able to control B. burgdorferi
infection and result in enhanced dissemination. This is important because preventing dissemination reduces
the probability of developing chronic disease. Our preliminary data demonstrate reduced blood neutrophils and
platelets in mice co-infected with both Bb and an intracellular organism Ehrlichia muris, relative to mice
infected with B. burgdorferi alone. We propose two related, but independent aims. In Aim 1 we will investigate
the specific role of neutropenia, induced by co-infection, on B. burgdorferi dissemination. In Aim 2 we address
the impact of thrombocytopenia and platelets on B. burgdorferi dissemination. This proof-of-concept work will
address how infection with one pathogen enhances the infection, and dissemination, of another pathogen
during tick-borne co-infection. Enhanced dissemination and infection of such tissues as the brain and heart are
critical early events that induce susceptibility to long term complications. Information learned from these
studies will define mechanisms of host defense against tick-borne co-infection, and may ultimately lead to
novel therapies to prevent B. burgdorferi dissemination, which will reduce long-term complications such as
carditis and arthritis.