Babesia microti and Borrelia burgdorferi Co-infection in Mice
- Ray Sullivan
- 4 minutes ago
- 3 min read
Tick-borne co-infections are an escalating concern in endemic regions worldwide, notably in the United States, where the protozoan Babesia microti and the bacterium Borrelia burgdorferi are frequently co-transmitted by Ixodes ticks. While the acute phase interactions of these pathogens have been explored, their long-term persistence and reciprocal effects on disease pathogenesis in a murine model remained a gap. A recent 16-week infection study in C3H/HeJ mice sheds light on these complex host-microbial dynamics, offering crucial insights for vaccine development and therapeutic management of co-infected individuals. The work was published by Rocha et al., in Nikhat Parveen’s Lab at the Rutgers New Jersey Medical School, along with from a colleague from Washington State University.
The study utilized C3H/HeJ mice, a strain chosen for its TLR4 gene mutation, which makes it particularly susceptible to pronounced Lyme disease symptoms, mirroring the systemic nature of Lyme disease in humans. These mice were inoculated with either Borrelia burgdorferi (N40 strain), Babesia microti (Gray strain), or both, and monitored for up to 16 weeks. Pathogen burdens were tracked using live imaging (IVIS-200) for bioluminescent Borrelia burgdorferi and Giemsa-stained blood smears for Babesia microti parasitemia. Furthermore, the study assessed disease manifestations like splenomegaly, blood-brain barrier (BBB) integrity using Evans Blue dye, and Lyme arthritis through histopathological analysis of joint sections.
Key Findings Illuminating Long-Term Co-infection Dynamics:
Both Babesia microti and Borrelia burgdorferi demonstrated long-term survival in the mice, detectable even after 16 weeks post-infection. Specifically, a low level of microscopically detectable Babesia microti parasitemia (<1% infected red blood cells) persisted in all infected groups at 16 weeks. Borrelia burgdorferi colonization was also consistently detected until 16 weeks.
Reciprocal Effects on Pathogen Burden:
Borrelia burgdorferi attenuates Babesia microti parasitemia: In co-infected mice, peak Babesia microti parasitemia was significantly lower compared to mice infected with Babesia microti alone, particularly evident in male mice at the acute phase (3 weeks post-infection). This suggests that Borrelia burgdorferi infection, especially with the invasive N40 strain, might stimulate an innate immune response that controls Babesia microti parasitemia.
Babesia microti initially increases Borrelia burgdorferi burden: At the acute phase (2 weeks), co-infected mice showed higher bioluminescent signal intensity for Borrelia burgdorferi colonization, indicating an increased burden. However, this effect did not persist long-term, normalizing in later stages (4, 8, and 16 weeks).
Splenomegaly (enlarged spleen), a hallmark of babesiosis, was observed in both sexes at 16 weeks in B. microti-infected groups. However, it was significantly higher and persisted only in female mice that were solely infected with Babesia microti or co-infected. In male mice, splenomegaly largely resolved by 16 weeks. This highlights a potential sex-based difference in chronic disease manifestations.
The study found that Babesia microti infection, both alone and in co-infection, compromised the integrity of the BBB in mice at the acute phase (2 weeks). This mirrors observations in cerebral malaria caused by the protozoan Plasmodium falciparum. In contrast, Borrelia burgdorferi infection alone did not disrupt the BBB. Borrelia burgdorferi was detected colonizing the dura mater, tough outer layer of tissue that covers and protects the brain and spinal cord and is closest to the skull. However, direct penetration into the dense brain tissue was not clearly demonstrated by live imaging. This finding suggests that Babesia microti could potentially facilitate other pathogens, like Borrelia burgdorferi, in accessing the central nervous system (CNS), potentially contributing to neuroborreliosis.
Lyme inflammatory arthritis was most pronounced at 4 weeks post-infection, with significant leukocyte infiltration in joints of Borrelia burgdorferi-infected and co-infected mice. While the burden of spirochetes was reduced by 4 weeks, inflammation persisted until 16 weeks in some cases, likely due to persistent pro-inflammatory antigens from dead spirochetes. The severity of arthritis was comparable between Borrelia burgdorferi alone and co-infected groups at 4 and 16 weeks, though prior acute-phase studies reported exacerbation with co-infection.
This study underscores the complex and stage-dependent interactions between Babesia microti and Borrelia burgdorferi. The findings contribute significantly to understanding the pathogenicity of these tick-borne co-infections and provide data for developing more effective vaccines and successful antimicrobial strategies. The persistent splenomegaly in females, the transient enhancement of Borrelia burgdorferi burden by Babesia microti, and particularly the BBB disruption by Babesia microti, highlight avenues for future research to elucidate the mechanisms underlying severe and chronic manifestations in co-infected patients.
Rocha SC, Moustafa MAM, Velásquez CV, Azuama OC, Zafar K, Meyer C, Araujo M, Taylor K, Parveen N. Long-term survival of Babesia microti and Borrelia burgdorferi in C3H/HeJ mice and their effect on Lyme arthritis and babesiosis manifestations. Microbiol Spectr. 2025 Aug 12:e0025225. doi: 10.1128/spectrum.00252-25. Epub ahead of print. PMID: 40793757.