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Host transcriptome response to Borrelia burgdorferi sensu lato.

ABSTRACT: The host immune response to infection is a well-coordinated system of innate and adaptive immune cells working in concert to prevent the colonization and dissemination of a pathogen. While this typically leads to a beneficial outcome and the suppression of disease pathogenesis, the Lyme borreliosis bacterium, Borrelia burgdorferi sensu lato, can elicit an immune profile that leads to a deleterious state. As B. burgdorferi s.l. produces no known toxins, it is suggested that the immune and inflammatory response of the host are responsible for the manifestation of symptoms, including flu-like symptoms, musculoskeletal pain, and cognitive disorders. The past several years has seen a substantial increase in the use of microarray and sequencing technologies to investigate the transcriptome response induced by B. burgdorferi s.l., thus enabling researchers to identify key factors and pathways underlying the pathophysiology of Lyme borreliosis. In this review we present the major host transcriptional outcomes induced by the bacterium across several studies and discuss the overarching theme of the host inflammatory and immune response, and how it influences the pathology of Lyme borreliosis.

SUBMITTER: Thompson D

PROVIDER: S-EPMC8127729 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Host transcriptome response to Borrelia burgdorferi sensu lato.

Thompson Derick D Watt John A JA Brissette Catherine A CA

Ticks and tick-borne diseases 20201213 2

The host immune response to infection is a well-coordinated system of innate and adaptive immune cells working in concert to prevent the colonization and dissemination of a pathogen. While this typically leads to a beneficial outcome and the suppression of disease pathogenesis, the Lyme borreliosis bacterium, Borrelia burgdorferi sensu lato, can elicit an immune profile that leads to a deleterious state. As B. burgdorferi s.l. produces no known toxins, it is suggested that the immune and inflamm ...[more]

PMID: 33360384

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Project description:The causative agents of Lyme borreliosis, spirochetes belonging to the Borrelia burgdorferi sensu lato group, have developed several ways to protect themselves against killing by the host complement system. In addition, it has been shown that serum sensitive isolates are (partially) protected by the Ixodes Tick Salivary Lectin Pathway Inhibitor (TSLPI) protein; a salivary gland protein that inhibits the function of Mannose Binding Lectin (MBL). MBL is a C-type lectin that recognizes oligosaccharides on pathogens and activates the complement system via the lectin pathway. MBL deficiency has been linked to a more severe course of several infectious diseases and humans with detectable antibodies against B. burgdorferi are significantly more often MBL deficient compared to humans without antibodies against B. burgdorferi. Here we set out to investigate the role of MBL in the immune response against B. burgdorferi in more detail. We demonstrate that B. burgdorferi N40 needle-infected C57BL/6 MBL deficient mice harbored significantly higher B. burgdorferi numbers in skin tissue during the early course of infection. In line with these findings they also developed higher anti-B. burgdorferi IgG serum antibodies compared to WT controls. In contrast, B. burgdorferi loads in distant tissue such as heart, joints or bladder at later time points were similar for both mouse strains. These in vivo findings were corroborated using a B. burgdorferi N40-infected I. scapularis infestation model. We showed that MBL is capable of binding B. burgdorferi through its carbohydrate recognition domains, but in vitro complement killing assays, peritoneal macrophage and whole blood stimulations, phagocytosis assays and an in vivo migration experiment did not reveal the mechanism by which MBL facilitates early clearance of B. burgdorferi. To conclude, we show a protective role of MBL in the early stages of B. burgdorferi infection, yet the underlying mechanism warrants further investigation.

Project description:BackgroundThe Borrelia burgdorferi sensu lato (s.l.) species complex consists of tick-transmitted bacteria and currently comprises approximately 20 named and proposed genospecies some of which are known to cause Lyme Borreliosis. Species have been defined via genetic distances and ecological niches they occupy. Understanding the evolutionary relationship of species of the complex is fundamental to explaining patterns of speciation. This in turn forms a crucial basis to frame testable hypotheses concerning the underlying processes including host and vector adaptations.ResultsIllumina Technology was used to obtain genome-wide sequence data for 93 strains of 14 named genospecies of the B. burgdorferi species complex and genomic data already published for 18 additional strain (including one new species) was added. Phylogenetic reconstruction based on 114 orthologous single copy genes shows that the genospecies represent clearly distinguishable taxa with recent and still ongoing speciation events apparent in Europe and Asia. The position of Borrelia species in the phylogeny is consistent with host associations constituting a major driver for speciation. Interestingly, the data also demonstrate that vector associations are an additional driver for diversification in this tick-borne species complex. This is particularly obvious in B. bavariensis, a rodent adapted species that has diverged from the bird-associated B. garinii most likely in Asia. It now consists of two populations one of which most probably invaded Europe following adaptation to a new vector (Ixodes ricinus) and currently expands its distribution range.ConclusionsThe results imply that genotypes/species with novel properties regarding host or vector associations have evolved recurrently during the history of the species complex and may emerge at any time. We suggest that the finding of vector associations as a driver for diversification may be a general pattern for tick-borne pathogens. The core genome analysis presented here provides an important source for investigations of the underlying mechanisms of speciation in tick-borne pathogens.

Dataset Information

Host transcriptome response to Borrelia burgdorferi sensu lato.

Publications

Host transcriptome response to Borrelia burgdorferi sensu lato.

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