Abstract
Lyme disease is the most prominent tick-borne disease in the United States. Co-infections with the tick-transmitted pathogens Babesia microti and Borrelia burgdorferi sensu stricto are becoming a serious health problem. B. burgdorferi is an extracellular spirochete that causes Lyme disease while B. microti is a protozoan that infects erythrocytes and causes babesiosis. Testing of donated blood for Babesia species is not currently mandatory due to unavailability of an FDA approved test. Transmission of this protozoan by blood transfusion often results in high morbidity and mortality in recipients. Infection of C3H/HeJ mice with B. burgdorferi and B. microti individually results in inflammatory Lyme disease and display of human babesiosis-like symptoms, respectively. Here we use this mouse model to provide a detailed investigation of the reciprocal influence of the two pathogens on each other during co-infection. We show that B. burgdorferi infection attenuates parasitemia in mice while B. microti subverts the splenic immune response, such that a marked decrease in splenic B and T cells, reduction in antibody levels and diminished functional humoral immunity, as determined by spirochete opsonophagocytosis, are observed in co-infected mice compared to only B. burgdorferi infected mice. Furthermore, immunosuppression by B. microti in co-infected mice showed an association with enhanced Lyme disease manifestations. This study demonstrates the effect of only simultaneous infection by B. burgdorferi and B. microti on each pathogen, immune response and on disease manifestations with respect to infection by the spirochete and the parasite. In our future studies, we will examine the overall effects of sequential infection by these pathogens on host immune responses and disease outcomes.
Highlights
The Centers of Disease Control and Prevention (CDC) estimates that ∼300,000 cases of Lyme disease and ∼2000 cases of human babesiosis occur in the United States annually, while ∼65,000 cases of Lyme disease are reported occur in Europe per year (Moore et al, 2016; Primus et al, 2018)
We investigated the impact of splenic immune responses on the resolution of B. microti parasitemia at the acute phase of co-infection with B. burgdorferi
The Institutional Animal Care and Use Committee (IACUC) members reviewed and approved the protocol number PROTO201702491 entitled, “Spirochetes and tick-borne pathogens,” of the corresponding author to conduct this study at Rutgers New Jersey Medical School following guidelines of the Animal Welfare Act, The Institute of Laboratory Animal Resources Guide for the Care and Use of Laboratory Animals, and the Public Health Service Policy that are fully adopted at the Rutgers University
Summary
The Centers of Disease Control and Prevention (CDC) estimates that ∼300,000 cases of Lyme disease and ∼2000 cases of human babesiosis occur in the United States annually, while ∼65,000 cases of Lyme disease are reported occur in Europe per year (Moore et al, 2016; Primus et al, 2018). Babesia microti Infection Exacerbates Lyme Disease under-reporting of Lyme disease in Europe (Muller et al, 2012). In the United States, Lyme arthritis is the most common persistent manifestation while acrodermatitis and severe neuroborreliosis are more common in Europe (Jungnick et al, 2015; Steere et al, 2016). The protozoan parasites, Babesia microti and Babesia divergens are the major causes of human babesiosis in the United States and Europe, respectively. Babesiosis is generally asymptomatic in healthy individuals, which often results in establishment of a carrier state, such that donation of blood by infected, asymptomatic individuals can lead to transfusiontransmitted babesiosis (Krause et al, 1998, 2008), making this disease a serious health concern
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