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Human Fc?-receptor IIb modulates pathogen-specific versus self-reactive antibody responses in lyme arthritis.

ABSTRACT: Pathogen-specific antibody responses need to be tightly regulated to generate protective but limit self-reactive immune responses. While loss of humoral tolerance has been associated with microbial infections, the pathways involved in balancing protective versus autoreactive antibody responses in humans are incompletely understood. Studies in classical mouse model systems have provided evidence that balancing of immune responses through inhibitory receptors is an important quality control checkpoint. Genetic differences between inbred mouse models and the outbred human population and allelic receptor variants not present in mice; however, argue for caution when directly translating these findings to the human system. By studying Borrelia burgdorferi infection in humanized mice reconstituted with human hematopoietic stem cells from donors homozygous for a functional or a non-functional Fc?RIIb allele, we show that the human inhibitory Fc?RIIb is a critical checkpoint balancing protective and autoreactive immune responses, linking infection with induction of autoimmunity in the human immune system.

SUBMITTER: Danzer H

PROVIDER: S-EPMC7438111 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Human Fcγ-receptor IIb modulates pathogen-specific versus self-reactive antibody responses in lyme arthritis.

Danzer Heike H Glaesner Joachim J Baerenwaldt Anne A Reitinger Carmen C Lux Anja A Heger Lukas L Dudziak Diana D Harrer Thomas T Gessner André A Nimmerjahn Falk F

eLife 20200702

Pathogen-specific antibody responses need to be tightly regulated to generate protective but limit self-reactive immune responses. While loss of humoral tolerance has been associated with microbial infections, the pathways involved in balancing protective versus autoreactive antibody responses in humans are incompletely understood. Studies in classical mouse model systems have provided evidence that balancing of immune responses through inhibitory receptors is an important quality control checkp ...[more]

PMID: 32613944

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Project description:BACKGROUND:Forests in urban landscapes differ from their rural counterparts in ways that may alter vector-borne disease dynamics. In urban forest fragments, tick-borne pathogen prevalence is not well characterized; mitigating disease risk in densely-populated urban landscapes requires understanding ecological factors that affect pathogen prevalence. We trapped blacklegged tick (Ixodes scapularis) nymphs in urban forest fragments on the East Coast of the United States and used multiplex real-time PCR assays to quantify the prevalence of four zoonotic, tick-borne pathogens. We used Bayesian logistic regression and WAIC model selection to understand how vegetation, habitat, and landscape features of urban forests relate to the prevalence of B. burgdorferi (the causative agent of Lyme disease) among blacklegged ticks. RESULTS:In the 258 nymphs tested, we detected Borrelia burgdorferi (11.2% of ticks), Borrelia miyamotoi (0.8%) and Anaplasma phagocytophilum (1.9%), but we did not find Babesia microti (0%). Ticks collected from forests invaded by non-native multiflora rose (Rosa multiflora) had greater B. burgdorferi infection rates (mean?=?15.9%) than ticks collected from uninvaded forests (mean?=?7.9%). Overall, B. burgdorferi prevalence among ticks was positively related to habitat features (e.g. coarse woody debris and total understory cover) favorable for competent reservoir host species. CONCLUSIONS:Understory structure provided by non-native, invasive shrubs appears to aggregate ticks and reservoir hosts, increasing opportunities for pathogen transmission. However, when we consider pathogen prevalence among nymphs in context with relative abundance of questing nymphs, invasive plants do not necessarily increase disease risk. Although pathogen prevalence is greater among ticks in invaded forests, the probability of encountering an infected tick remains greater in uninvaded forests characterized by thick litter layers, sparse understories, and relatively greater questing tick abundance in urban landscapes.

Dataset Information

Human Fc?-receptor IIb modulates pathogen-specific versus self-reactive antibody responses in lyme arthritis.

Publications

Human Fcγ-receptor IIb modulates pathogen-specific versus self-reactive antibody responses in lyme arthritis.

Similar Datasets

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