Interactions between host immune response and antigenic variation that control Borrelia burgdorferi population dynamics

Zhou, Wei; Brisson, Dustin

doi:10.1099/mic.0.000513

Cited by 5 publications

(5 citation statements)

References 42 publications

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“…This may also be partially responsible for higher heart and joint burden, as antibody responses help combat B . burgdorferi infection [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

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A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis

Gupta¹,

Arora²,

Kloos³

et al. 2020

PLoS Pathog

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Lyme disease, the most common vector-borne illness in North America, is caused by the spirochete Borrelia burgdorferi. Infection begins in the skin following a tick bite and can spread to the hearts, joints, nervous system, and other organs. Diverse host responses influence the level of B. burgdorferi infection in mice and humans. Using a systems biology approach, we examined potential molecular interactions between human extracellular and secreted proteins and B. burgdorferi. A yeast display library expressing 1031 human extracellular proteins was probed against 36 isolates of B. burgdorferi sensu lato. We found that human Peptidoglycan Recognition Protein 1 (PGLYRP1) interacted with the vast majority of B. burgdorferi isolates. In subsequent experiments, we demonstrated that recombinant PGLYRP1 interacts with purified B. burgdorferi peptidoglycan and exhibits borreliacidal activity, suggesting that vertebrate hosts may use PGLYRP1 to identify B. burgdorferi. We examined B. burgdorferi infection in mice lacking PGLYRP1 and observed an increased spirochete burden in the heart and joints, along with splenomegaly. Mice lacking PGLYRP1 also showed signs of immune dysregulation, including lower serum IgG levels and higher levels of IFNγ, CXCL9, and CXCL10.Taken together, our findings suggest that PGLYRP1 plays a role in the host’s response to B. burgdorferi and further demonstrate the utility of expansive yeast display screening in capturing biologically relevant interactions between spirochetes and their hosts.

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“…This may also be partially responsible for higher heart and joint burden, as antibody responses help combat B . burgdorferi infection [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…The alteration in antibody responses against B. burgdorferi, observed in PGLYRP1 -/mice also suggests a role for this protein in adaptive immune responses. This may also be partially responsible for higher heart and joint burden, as antibody responses help combat B. burgdorferi infection [48,49].…”

Section: Plos Pathogensmentioning

confidence: 99%

A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis

Gupta¹,

Arora²,

Kloos³

et al. 2020

PLoS Pathog

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“…The elimination of pathogens by host immune responses is a major bottleneck of infectivity, limiting the breadth of host competence [ 9 , 11 , 12 ]. Complement is one of the first lines of host defenses in vertebrate animals and can be activated through three canonical routes: the classical, lectin, and alternative pathways [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system

et al. 2021

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Pathogens possess the ability to adapt and survive in some host species but not in others–an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement, a defense in vertebrate blood, and a polymorphic bacterial protein, CspA, which inactivates complement by binding to a host complement inhibitor, Factor H (FH). CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. CspA is the only member of the Pfam54 gene family to exhibit host-specific FH-binding. Phylogenetic analyses revealed convergent evolution as the driver of such uniqueness, and that FH-binding likely emerged during the last glacial maximum. Our results identify a determinant of host tropism in Lyme disease infection, thus defining an evolutionary mechanism that shapes host-pathogen associations.

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“…The elimination of microparasites by host immune responses is a major bottleneck of infectivity, limiting the breadth of host competence (9, 11, 12). Complement is one of the first lines of host defenses in vertebrate animals and can be activated through three canonical routes: the classical, lectin, and alternative pathways (13).…”

Section: Introductionmentioning

confidence: 99%

Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system

Hart

Dupuis

Tufts

et al. 2021

Preprint

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Microparasites selectively adapt in some hosts, known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. LD bacteria species vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different LD bacteria species, utilizing feeding chambers and live mice and quail, we found species-level differences of bacterial transmission. These differences localize on the tick blood meal, and complement, a defense in vertebrate blood, and a bacterial polymorphic protein, CspA, which inactivates complement by binding to a host complement inhibitor, FH. CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. Phylogenetic analyses revealed convergent evolution as the driver of such findings, which likely emerged during the last glacial maximum. Our results identify LD bacterial determinants of host tropism, defining an evolutionary mechanism that shapes host-microparasite associations.

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Interactions between host immune response and antigenic variation that control Borrelia burgdorferi population dynamics

Cited by 5 publications

References 42 publications

A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis

A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis

Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system

Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system

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