Biology subjects

Belperron, A. A.

Publications and source records attributed to Belperron, A. A..

3 recordsLinked to original sources

bioRxiv2025

Single cell immunophenotyping identifies CD8+ GZMK+ IFNG+ T cells as a key immune population in cutaneous Lyme disease

The skin lesion erythema migrans (EM) is the first clinical sign of Lyme disease, an infection due to the tick-transmitted bacterium Borrelia burgdorferi (Bb). Previously, we used scRNA-Seq to characterize the cutaneous immune response in the EM lesion, focusing on B cells. Here, with an expanded sample size, we profiled T cell responses in EM lesions compared to autologous uninvolved skin. In addition to CD4+ T cell subsets known to be abundant in the EM, we identified clonal expansion of CD8+ GZMK+ IFNG+ T cells that exhibited significant differential expression of interferon-regulated genes. This subset included IFNG+ cells with low cytotoxic gene expression, which may promote inflammation. While FOXP3+ regulatory T cells were also increased in EM, they exhibited little IL10 expression. In contrast, a CD4+ FOXP3- tissue-resident T cell subset contained the largest population of cells with IL10 expression. Fibroblasts, endothelial cells, and pericytes were the principal cells that significantly differentially expressed key T cell-recruiting chemokines. These studies represent the first comprehensive interrogation of the cutaneous T cell response to Bb infection using single cell transcriptomics with adaptive immune receptor sequencing, providing insight into the skin barrier defense and orchestration of the immune response to this vector-borne pathogen.

immunology↗

bioRxiv2024

Secretory leukocyte protease inhibitor influences periarticular joint inflammation in B. burgdorferi-infected mice

Lyme disease, caused by Borrelia burgdorferi, is the most common tick-borne infection in the United States. Arthritis is a major clinical manifestation of infection, and synovial tissue damage has been attributed to the excessive pro-inflammatory responses. The secretory leukocyte protease inhibitor (SLPI) promotes tissue repair and exerts anti-inflammatory effects. The role of SLPI in the development of Lyme arthritis in C57BL/6 mice, which can be infected with B. burgdorferi, but only develop mild joint inflammation, was therefore examined. SLPI-deficient C57BL/6 mice challenged with B. burgdorferi had a higher infection load in the tibiotarsal joints and marked periarticular swelling, compared to infected wild type control mice. The ankle joint tissues of B. burgdorferi-infected SLPI-deficient mice contained significantly higher percentages of infiltrating neutrophils and macrophages. B. burgdorferi-infected SLPI-deficient mice also exhibited elevated serum levels of IL-6, neutrophil elastase, and MMP-8. Moreover, using a recently developed BASEHIT (BActerial Selection to Elucidate Host-microbe Interactions in high Throughput) library, we found that SLPI directly interacts with B. burgdorferi. These data demonstrate the importance of SLPI in suppressing periarticular joint inflammation in Lyme disease.

microbiology↗

bioRxiv2020

Proteomics on longitudinal serum samples differentiates localized and disseminated Lyme disease

Lyme disease (LD) is the most prevalent vector-borne disease in North America, with ~300,000 new cases annually in the USA alone. LD is most often recognized by the appearance of the skin lesion erythema migrans (EM) at the tick bite site but also can present with signs of disseminated infection manifesting as multiple EM lesions and/or involvement of the heart, nervous system or joints. In this study, we examined the serum proteome of study participants presenting with either a single EM (localized LD) or early disseminated infection (disseminated LD). Samples collected at the time of diagnosis and at convalescent time points were assessed using our in-house developed MStern blotting-based serum proteomics platform. After technical validation of our platform, the temporal analysis from diagnosis to clinical resolution of the infection demonstrates LD stage-associated pathways activation such as a temporary upregulation of acute phase response specific to the participants with disseminated LD. In addition, we identified the members of the serum amyloid A protein family as potentially promising candidate biomarkers to identify those with disseminated LD. The results of this pilot study demonstrate the feasibility of using our time- and cost-effective sample sparing MStern blotting-based serum proteomics platform to efficiently interrogate proteome changes over time in those suffering infections such as LD. These observations establish a new approach to human serum proteomics, provide fresh insight into the host immune responses associated with disease severity (localized versus disseminated infection) and suggest novel biomarker candidate panels for LD stages. ImportanceWe investigated the proteome changes of Borrelia burgdorferi-infected participants with either a single erythema migrans or early disseminated Lyme disease infection. Using our in-house time-and cost-effective proteomics platform, the temporal analysis from diagnosis to clinical resolution of the infection shows a temporary upregulation of the acute phase response specific to the participants with disseminated infection. Finally, specific protein panels were identified as possible biomarker candidates to categorize those having an initial diagnosis of disseminated manifestation using a reference cohort of acute localized infection and a clinically resolved convalescent phase disease samples from the same Lyme disease participants.

immunology↗