Biology subjects

Batteux, F.

Publications and source records attributed to Batteux, F..

5 recordsLinked to original sources

bioRxiv2026

Serotypic heterogeneity in the response to pneumococcal vaccine

The assessment of pneumococcal vaccine response currently relies on a single IgG concentration threshold, identical for all serotypes, as recommended by the WHO and AAAAI. However, the recommended thresholds do not take the wide inter-serotype variability into account. The purpose of this study was to determine if the antibody threshold linked to a functional immune response varies according to serotype. We performed a retrospective analysis on 729 samples from adults at risk of invasive pneumococcal disease (IPD), sent between 2018 and 2024 to assess vaccine response. Specific IgG concentrations for seven vaccine serotypes were measured by ELISA and compared to opsonophagocytic assay (OPA) results, a functional test considered as the gold standard. For each serotype, we determined the most predictive IgG concentration (PIC) for a positive OPA result using ROC curves, Youdens index, and bootstrap analysis with 1,000 resamples. The resulting PIC were then compared using non-parametric tests (Kruskal-Wallis test followed by Dunns post-hoc test with Holms correction). The PIC varied considerably among serotypes, ranging from 0.84 to 4.74 {micro}g/mL. This variability was found to be statistically significant (p<0.0001). Areas Under the Curve (AUC), ranging from 0.73 to 0.87, demonstrate good diagnostic performance. Overall, the application of serotype-specific thresholds in patients significantly change the classification of vaccination status compared to a single threshold (Cochran, McNemar). These results indicate that the protective antibody threshold is not universal. A serotype-specific approach would allow a more precise and relevant assessment of the pneumococcal vaccine response. Author summaryThe introduction of the 7-valent pneumococcal conjugate vaccine (PCV-7) in the early 2000s significantly changed the epidemiology of invasive pneumococcal disease by modifying serotype distribution. However, vaccine-induced immunity varies across serotypes, and this heterogeneity remains incompletely understood. In this study, we first assessed differences in vaccine responses according to serotype. We then determined predictive serotype-specific immunoglobulin concentration for the seven routinely serotypes tested in our laboratory, defined as the minimal levels required to induce a positive opsonophagocytic activity (OPA) response. The results enable a more accurate assessment of serotype-specific vaccine immunity, supporting improved patient stratification and guiding booster vaccination in individuals with insufficient responses.

immunology↗

bioRxiv2026

Preconceptional immunomodulation partially corrects pregnancy associated abnormalities induced by endometriosis in a mice model, with a normalization of transcriptional alteration observed in the developing fetal maternal interface at the single cell level.

Endometriosis is a chronic disease of gynaecological origin that affects approximately 10% of women worldwide and has a significant impact on patients lives. Women with endometriosis attempting to conceive may experience infertility and have a higher risk of obstetric complications. They are also more likely to miscarry and have placental defects during pregnancy. The impact of endometriosis on pregnancy remains unclear. Defects in implantation and placentation may be present, but these processes are difficult to study in human subjects. To address this issue, we used a surgically induced mouse model of endometriosis and examined pregnancy in the CBAxDBA crossbreed, which is commonly employed to study pregnancy immunology. We examined early (E9.5) and late (E18.5) gestational stages. In this model, we confirmed that the presence of endometriosis-like lesions resulted in fewer implantations and a higher proportion of fetal resorption, which is analogous to miscarriage. When an immune tolerance was induced previous to the endometriosis induction, we observed that endometriotic lesions were smaller, and gestational complications were mostly corrected. At early gestation (E9.5), fetal-maternal interfaces were retrieved to assess the potential impact of endometriosis and immunomodulation on placental development using single-cell RNA-sequencing. Our data show that most changes induced by endometriosis occur in decidual stromal cells, which originate from the endometrium. In these cells, we observed a consistent upregulation of Gata4, a transcription factor previously found to be elevated in the endometrium of women with endometriosis. We also observed downregulation of Prap1, which is an indicator of uterine receptivity and successful implantation in mice. In the mice where immune tolerance was induced, the endometriosis associated transcriptomic changes were partially reversed. In immune cells, endometriosis leads to an inflammation-associated signature. Additionally, the interferon gamma response is reduced in NK cells, which has been shown to be crucial for spiral artery remodelling and decidual integrity, which may be involved in the observed increased resorption rate. Overall, our findings provide new insights into endometriosis-associated infertility and pregnancy complications in a mouse model that can be partially corrected by immune modulation. These results suggest that targeting the immune system should be considered in future studies to improve pregnancy outcomes in patients with endometriosis.

molecular biology↗

bioRxiv2022

Mechanistic target of rapamycin (mTOR) regulates self-sustained quiescence, tumor indolence and late clinical metastasis in a Beclin-1-dependent manner.

Self-sustained quiescence (SSQ) has been characterized as a stable but reversible non-proliferative cellular state that limits the cloning of cultured cancer cells. By developing refined clonogenic assays, we showed here that cancer cells in SSQ can be selected with anticancer agents and that culture at low cell density induced SSQ in pancreas and prostate adenocarcinoma cells. Pre-culture of cells in 3D or their pretreatment with pharmacological inhibitors of mechanistic target of rapamycin (mTOR) synergize with low cell density for induction of SSQ in a Beclin-1-dependent manner. Dissociated pancreatic adenocarcinoma (PAAD) cells rendered defective for SSQ by down-regulating Beclin-1 expression exhibit higher tumor growth rate when injected subcutaneously into mice. Conversely, dissociated PAAD cells in SSQ promote the formation of small indolent tumors that eventually transitioned to a rapid growth phase. Ex vivo clonogenic assays showed that up to 40% of clonogenic cancer cells enzymatically dissociated from resected fast-growing tumors could enter SSQ, suggesting that SSQ could significantly impact the proliferation of cancer cells that are naturally dispersed from tumors. Remarkably, the kinetics of clinical metastatic recurrence in 124 patients with pancreatic adenocarcinoma included in the TGCA-PAAD project could be predicted from Beclin-1 and Cyclin-A2 mRNA levels in their primary tumor, Cyclin A2 mRNA being a marker of both cell proliferation and mTOR complex 1 activity. Overall, our data show that SSQ is likely to promote the late development of clinical metastases and suggest that identifying new agents targeting cancer cells in SSQ could help improve patient survival.

cancer biology↗

bioRxiv2020

Human T-bet governs innate and innate-like adaptive IFN-γ immunity against mycobacteria

Inborn errors of human IFN-{gamma} immunity underlie mycobacterial disease. We report a patient with mycobacterial disease due to an inherited deficiency of the transcription factor T-bet. This deficiency abolishes the expression of T-bet target genes, including IFNG, by altering chromatin accessibility and DNA methylation in CD4+ T cells. The patient has profoundly diminished counts of mycobacterial-reactive circulating NK, invariant NKT (iNKT), mucosal-associated invariant T (MAIT), and V{delta}2+ {gamma}{delta} T lymphocytes, and of non-mycobacterial-reactive classic TH1 lymphocytes, the remainders of which also produce abnormally low amounts of IFN-{gamma}. Other IFN-{gamma}-producing lymphocyte subsets however develop normally, but with low levels of IFN-{gamma} production, with exception of V{delta}2- {gamma}{delta} T lymphocytes, which produce normal amounts of IFN-{gamma} in response to non-mycobacterial stimulation, and non-classic TH1 (TH1*) lymphocytes, which produce IFN-{gamma} normally in response to mycobacterial antigens. Human T-bet deficiency thus underlies mycobacterial disease by preventing the development of, and IFN-{gamma} production by, innate (NK) and innate-like adaptive lymphocytes (iNKT, MAIT, and V{delta}2+ {gamma}{delta} T cells), with mycobacterial-specific, IFN-{gamma}-producing, purely adaptive {beta} TH1* cells unable to compensate for this deficit.

immunology↗

bioRxiv2018

TGF-b2, catalase activity, H2O2 output and metastatic potential of diverse types of tumour

Theileria annulata is a protozoan parasite that infects and transforms bovine macrophages causing a myeloid-leukaemia-like disease called tropical theileriosis. TGF-{beta}2 is highly expressed in many cancer cells and is significantly increased in Theileria-transformed macrophages, as are levels of Reactive Oxygen Species (ROS), notably H2O2. Here, we describe the interplay between TGF-{beta}2 and ROS in cellular transformation. We show that TGF-{beta}2 drives expression of catalase to reduce the amount of H2O2 produced by T. annulata-transformed bovine macrophages, as well as by human lung (A549) and colon cancer (HT-29) cell lines. Theileria-transformed macrophages attenuated for dissemination express less catalase and produce more H2O2, but regain both virulent migratory and matrigel traversal phenotypes when stimulated with TGF-{beta}2, or catalase that reduce H2O2 output. Increased H2O2 output therefore, underpins the aggressive dissemination phenotype of diverse tumour cell types, but in contrast, too much H2O2 can dampen dissemination.

cancer biology↗