bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.06.28.601233

Exploring Porphyromonas gingivalis Pathogenesis and Antibody Pool Effect Using a Novel Mouse Reproductive Model

Abstract

This study introduces a novel animal model consisting of two phases. In phase I, Balb/c mice received three intraperitoneal injections of antibodies and two subcutaneous challenges with Porphyromonas gingivalis. The mice were divided into seven groups: G1, G2, and G3 received a single monoclonal antibody targeting the major outer membrane protein RagB of P. gingivalis and infection; G4 was infected without antibody; G5 and G6 received a mixture of monoclonal antibodies and infection; and G7 served as the healthy control. In phase II, one male was paired with one female from the same group and one healthy female. Fertility was assessed using maximum body weight growth rate (MWGR) and alive pup rate (APR). Results indicated that the APR of neonatal mice in G5+G6 significantly lower than G1-G3 and G7 (P < 0.05). Similarly, the MWGR of G5+G6 significantly lower than G7 (P < 0.05). Notably, the APR and MWGR in G4, which received no antibody, were lower than in G7 but higher than in G5-G6. These findings suggest that a mixture of antibodies coexisting with P. gingivalis infection leads to more detrimental reproductive damage than infection alone. The so-called Antibody Pool Effect plays a role in the pathogenesis of P. gingivalis. Understanding the mechanisms of this immunopathological damage may provide insights into the correlation between P. gingivalis infection and systemic diseases.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Shi, X., Xu, M. X.. 2024-07-02. Exploring Porphyromonas gingivalis Pathogenesis and Antibody Pool Effect Using a Novel Mouse Reproductive Model. https://doi.org/10.1101/2024.06.28.601233

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

ACE-engineered human iPSC-derived neutrophils enhance host defense against multidrug-resistant bacterial infections

Severe neutropenia predisposes patients to life-threatening infections, while donor-dependent granulocyte transfusions are limited by availability and variable cell quality. Here, we engineered human induced pluripotent stem cells (iPSCs) to constitutively or inducibly express angiotensin-converting enzyme (ACE) and differentiated them into functional ACE-engineered neutrophils (ACE-iNeu). ACE expression enhanced granulocytic maturation, reactive oxygen species generation, inflammatory cytokine production, and antimicrobial signaling. ACE-iNeu exhibited enhanced bactericidal activity against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa. Following adoptive transfer into neutropenic mice, ACE-iNeu significantly reduced circulating and tissue bacterial burdens. Integrated metabolomic and transcriptomic analyses revealed ACE-associated alterations in adenine nucleotide abundance and developmental and inflammatory pathways. Together, these findings establish ACE engineering as a strategy to enhance the production and antimicrobial function of human iPSC-derived neutrophils and support further preclinical development of engineered granulocyte therapies for severe drug-resistant infections.

immunology↗

Tetravalent dengue mRNA vaccination orchestrates balanced four-serotype immunity with durable memory and protection in mice.

An effective dengue vaccine must establish durable immunity across four dengue virus (DENV) serotypes, evade antibody-dependent enhancement (ADE), and overcome immune imprinting from prior exposure. Here, we developed TetprM-E mRNA-LNP, a tetravalent vaccine comprising LNP-formulated nucleoside-modified mRNAs encoding DENV1-4 precursor membrane-envelope (prM-E) antigens, and evaluated its immunogenicity, durability, protection and breath across serotype-specific immune backgrounds. Three immunization strategies elicited neutralizing titers greater than 1:1500 against each serotype. Passive transfer of immune sera conferred 100% survival and reduced viremia after lethal DENV2 challenge in immunocompromised mice. Vaccination induced DENV envelope (env)-specific CD8+T cells and CD4-dependent germinal-center responses. DENV env-binding antibodies persisted for 34 weeks alongside DENV env-specific memory B cells. Vaccine-elicited sera showed no measurable in vitro ADE. Although monovalent priming initially biased antibody responses, TetprM-E mRNA-LNP vaccination broadened neutralization across DENV1-4 regardless of priming serotype. Together, TetprM-E mRNA-LNP elicits broad, durable, and protective immunity despite serologic constraints from pre-existing immunity.

immunology↗

The antagonism of sex chromosomes and sex hormones dictates outcomes in Th17 cell-mediated central nervous system autoimmunity.

Biological sex traits are shaped by the combined effects of both sex hormones and chromosomes. How these factors interact in sex-related autoimmune diseases, such as multiple sclerosis (MS), has been a subject of intense recent interest. Here, using the Four Core Genotype (FCG) mouse model, in which these two variables can be disentangled, we describe an antagonism between sex hormones and chromosomes that potently influences outcomes in T helper 17 (Th17)-driven progressive central nervous system (CNS) autoimmunity. Male gonadal hormones dampen disease severity, irrespective of sex chromosome complement, by promoting a Wnt/{beta}-catenin signaling program associated with a homeostatic, non-pathogenic Th17 phenotype. By contrast, XY chromosomal complement exacerbates Th17 pathogenicity in a recipient sex-dependent manner; we identify the X-linked molecule SUV39H1 as an inhibitor of inflammatory Th17 cell function. Unexpectedly, we found that hormonally and chromosomally female FCG Th17 cells induced far more severe disease than WT female counterparts despite being genetically identical, pointing to a parental imprinting effect in dictating Th17 cell pathogenicity. These latter investigations uncovered Runx2, a transcription factor previously linked to developmental programs, as a novel negative regulator of the pathogenicity of Th17 cells. Together, our findings establish biological sex as a multilayered regulator of Th17 pathogenicity, revealing distinct and sometimes opposing contributions of hormones, chromosomes, and parental inheritance.

immunology↗