Nature Communications. April 2026. Heritable immunization is a promising approach to controlling infectious diseases...

Infection and Immunity, June 2026. Acute Lyme disease is caused by a Borrelia infection and typically responds to antibiotic treatment, but post-infectious chronic symptoms are common. The precise origin of these post-treatment symptoms is unknown; dysregulation of immune responses raised during the initial infection is likely to contribute. Antilipid antibodies are associated with several autoimmune diseases and have been shown to arise in both acute and post-treatment Lyme disease. To assess the potential contribution of antilipid antibodies to Lyme disease pathology and their possible use as biomarkers of both acute and chronic disease, we performed a survey of patient sera for antilipid antibodies during and after Borrelia burgdorferi infection. Results were similar in cross-sectional and longitudinal samples drawn from two different biobanks. Three antiphospholipid antibodies were elevated during infection, with two (antiphosphatidic acid and antiphosphatidylserine) significantly elevated even at the day of diagnosis before seroconversion on conventional tests. A subset of patients with chronic symptoms is identifiable by persistent elevation in antiphosphatidylserine; these antibodies found in post-treatment Lyme disease were not found in a panel of sera from patients with look-alike autoimmune disorders. Persistent elevation in antiphosphatidylserine may drive autoimmune-like symptoms of Lyme disease in some patients and could serve as a biomarker for chronic disease. The detection of antiphospholipid antibodies induced early in infection could also improve the diagnosis of acute infections.

Infection and Immunity, Apr. 2025. Ixodes scapularis ticks are an important vector for at least seven tick-borne human pathogens, including a North American Lyme disease spirochete, Borrelia burgdorferi. The ability for these ticks to survive in nature is credited, in part, to their ability to feed on a variety of hosts without triggering an immune response capable of preventing tick feeding. While the ability of nymphal ticks to feed on a variety of hosts has been well documented, the host-parasite interactions between larval I. scapularis and different vertebrate hosts are relatively unexplored. Here we report on the changes in the vertebrate host transcriptome present at the larval tick bite site using the natural I. scapularis host Peromyscus leucopus, a non-natural rodent host, Mus musculus (BALB/c), and humans. We note substantially less evidence of activation of canonical proinflammatory pathways in P. leucopus compared to BALB/c mice and pronounced evidence of inflammation in humans. Pathway enrichment analyses revealed a particularly strong signature of interferon gamma, tumor necrosis factor, and interleukin 1 signaling at the BALB/c and human tick bite sites. We also note that bite sites on BALB/c mice and humans, but not deer mice, show activation of wound-healing pathways. These data provide molecular evidence of the coevolution between larval I. scapularis and P. leucopus and, in addition, expand our overall understanding of I. scapularis feeding.

Plos Pathogens, Dec. 2025. Lyme disease is caused by the host-adapted spirochete Borrelia burgdorferi. With a genome of only 1.5 mbp, B. burgdorferi is dependent on metabolites scavenged from their vertebrate and invertebrate hosts for growth. These scavenged nutrients include several lipid precursors: the spirochete is auxotrophic for fatty acids and cholesterol, and also accumulates environmental phospholipids. Comprehensive lipidomic analysis of B. burgdorferi by LC MS/MS was used to identify previously undescribed membrane components. These include some likely scavenged from the culture medium and some which may be synthesized de novo via unknown pathways. Changes in fatty acid composition as cells enter stationary phase suggest that scavenging of environmental lipids is preferential to de novo synthesis, while transcriptomics suggests that this may be due to the energetic cost of synthesizing glycerol phosphate precursors. In media supplemented with excess phospholipids, scavenged lipids can be found at high concentrations in cells, suggesting that the membranes of infecting bacteria are likely to be partly shaped by the host environment. Transcriptomic analysis also show a link between environmental lipids and the expression of virulence-associated surface lipoproteins including reciprocal regulation of ospA and ospC. Given that borrelial membrane lipids are known to be antigenic during infection, these findings identify potential new targets for the development of diagnostic tests or vaccines.

Frontiers in Immunology, Nov 2025. Introduction: Clinical presentation of Lyme disease is largely due to host immune response to infection. Previously, we identified a variant (1805GG) in the TLR1 gene, a key immune sensor for Borrelia burgdorferi, which was associated with excessive inflammation and severe disease. Herein we examined the mechanism by which this variant leads to dysregulated immunity.

Methods: We found that patients with post-infectious Lyme arthritis, a condition characterized by marked persistent synovitis in joints, have a higher frequency of TLR1-1805GG compared to those whose arthritis resolves with antibiotics. To explore the possibility that this genotype-phenotype association was due to excessive inflammation, we then tested the functional impact of TLR1-1805GG on inflammatory responses and immune tolerance in PBMCs with or without this SNP and in THP-1 cell lines lacking TLR1.

Results: In response to B. burgdorferi stimulation, PBMCs with TLR1-1805GG had greater transcriptional upregulation of ~1200 immune-related genes and significantly higher cytokine levels in supernatants compared to cells without this variant. Moreover, repeat B. burgdorferi stimulation, which mimics tolerogenic conditions during the infection, failed to induce innate immune tolerance in PBMCs with TLR1-1805GG, or in THP-1 cells lacking TLR1, resulting in seemingly unabated immune activation consistent with marked inflammation in Lyme arthritis joints.

Conclusions: These results suggest that excessive inflammation in patients with TLR1-1805GG variant appears to be due to immune dysregulation and inability to induce immune tolerance. The findings help explain how early events during the infection may contribute to sustained immune activation after antibiotics and point to the role of TLR1 signaling in immune regulation.

Ticks and Tick-borne Diseases, Nov 2025. Tolerance and resistance are two host eco-immunological strategies in response to microparasite invasion. In the strategy of “resistance”, host responses are induced to decrease microparasite replication while the “tolerance” strategy allows hosts coexistence with microparasites by minimizing responses to avoid immune-mediated damage. The causative agent of Lyme disease is a group of genotypically diverse bacterial species, Borrelia burgdorferi sensu lato (Bb), which is transmitted by Ixodes ticks and persists in different reservoir animals. In North America, eastern fence lizards (Sceloporus undulatus) can be fed on by Ixodes ticks but are incompetent to one genotype of Bb (i.e., ospC type A). However, field-collected lizards showed evidence of previous infection by Bb strains with undefined genotypes. Supporting this evidence, we introduced three genotypically different Bb strains individually to eastern fence lizards and found a Bb genotype-dependent manner of infectivity. We compared liver transcriptomics and observed elevated immune responses triggered by a lizard-incompetent Bb strain (strain B31). We showed two lizard-competent strains with one having no immunomodulation (strain B379) but the other developing upregulated immune responses (strain 297). These results suggest that genetic variation in microparasites both induces different host strategies for dealing with infection and determines microparasite fitness in the hosts. These findings demonstrate that Bb and eastern fence lizards can serve as a model to investigate the mechanisms underlying eco-immunological strategies of tolerance vs. resistance during host-microparasite interaction.