Biology subjects

Lemaitre, J.

Publications and source records attributed to Lemaitre, J..

7 recordsLinked to original sources

bioRxiv2026

Modeling how memory CD8 T cells can elicit post-treatment control of HIV infection

While most people living with HIV suffer progressive disease following cessation of antiretroviral therapy, a small fraction elicits lasting post-treatment control. Understanding the mechanisms underlying this control is key to devising effective HIV remission strategies. Although recent studies implicate memory CD8 T cells, how these cells establish lasting viremic control remains unknown. Here, we combine mathematical modeling and analysis of data from SIV-infected non-human primates to elucidate the underlying mechanisms. We recognized that sustained antigenic stimulation leads to heritable epigenetic remodeling of the CD8 T cell pool, impairing memory cell survivability. Antiretroviral therapy rapidly suppresses viremia, thereby arresting antigenic stimulation and preserving memory potential. The greater this preservation is, the better would be the memory recall response following viral rebound post-treatment. Our mathematical model based on this hypothesis predicts that post-treatment control is an alternative steady state to progressive infection, realized by strong memory-driven recall responses. Our model fits longitudinal virological data spanning the pre-, during-, and post-antiretroviral treatment phases of infection, and recapitulates the outcomes of progressive disease and long-term remission realized, the latter predominantly with early treatment initiation. It shows, consistently with data, that memory CD8 T cells could drive post-treatment control independently of the size of the latent reservoir, explaining how such control may be realized more widely than estimated with prevalent hypotheses. Our model further explains the existence of a window of treatment initiation times that maximizes the chances of post-treatment control. Finally, model predictions inform interventions targeting memory CD8 T cells for HIV remission.

immunology↗

bioRxiv2025

A retrospective analysis of 400 publications reveals patterns of irreproducibility across an entire life sciences research field

The ReproSci project retrospectively analyzed the conceptual replicability of 1006 claims from 400 papers published between 1959 and 2011 in the field of Drosophila immunity. This project attempts to provide a comprehensive assessment, 14 years later, of the replicability of nearly all publications across an entire scientific community in experimental life sciences. We found that 61% of claims were verified, while only 7% were directly challenged (not replicable), a replicability rate higher than previous assessments. Notably, 24% of claims had never been independently tested and remain unchallenged. We performed experimental validations of a selection of 45 unchallenged claim, that revealed that a significant fraction (38/45) of them is in fact non-replicable. We also found that high-impact journals and top-ranked institutions are more likely to publish challenged claims. In line with the reproducibility crisis narrative, the rates of both challenged and unchallenged claims increased over time, especially as the field gained popularity. We characterized the uneven distribution of irreplicability among first and last authors. Surprisingly, irreplicability rates were similar between PhD students and postdocs, and did not decrease with experience or publication count. However, group leaders, who had prior experience as first authors in another Drosophila immunity team, had lower irreplicability rates, underscoring the importance of early-career training. Finally, authors with a more exploratory, short-term engagement with the field exhibited slightly higher rates of challenged claims and a markedly higher proportion of unchallenged ones. While limited by its reliance on published literature, this systematic, field-wide retrospective study offers meaningful perspective into the ongoing discussion on reproducibility in experimental life sciences.

scientific communication and education↗

bioRxiv2025

Disease progression is associated with differential neutrophil maturation in Mycobacterium tuberculosis-infected macaques

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is associated with clinical diversity and outcomes ranging from latent TB to active TB with distinct pathophysiologies. However, our understanding of the innate immune mechanisms related to the protection or progression of TB is limited. Among innate immune cells, the role of neutrophils is not fully elucidated, as they have been shown to exhibit both protective and harmful capacities in TB. This duality suggests possible differences in the nature and type of neutrophils present during the infection, generating different effects. We hypothesized that Mtb infection induces changes in neutrophil phenotype and function, influencing the infection outcomes. In order to decipher the link between neutrophils and disease progression, we used a cynomolgus macaque model of human TB. Based on clinical, bacteriological, and positron emission tomography with X-ray computed tomography (PET/CT) scan parameters, animals were stratified into two categories: animals that rapidly progressed to an active form of TB, designated as "fast progressors", and "slow progressors", which include low symptomatic or asymptomatic animals. In this study, we identified transcriptomic signatures of type I interferons and neutrophil degranulation in macaques with fast progression to active TB, which were not observed in animals with slow TB progression. Unsuppervised mass cytometry analysis showed the emergence of blood immature neutrophils (CD101+ CD10-) in fast progressing animals. In addition, circulating neutrophils from infected animals displayed capacities to modulate TNF- production and cytotoxic function of CD8 T cells in a contact-dependent mechanism. In the lungs, neutrophils infiltration in granuloma was higher in fast progressors and specifically located in the lymphocyte-rich region in lesions. These data suggest that specific neutrophil subpopulations are associated with disease progression. Furthermore, these data suggest that neutrophils may modulate CD8 T cells functions, which in turn contribute to the loss of Mtb control and fuel inflammation. AUTHORS SUMMARYMycobacterium tuberculosis (Mtb) infection in humans is associated with a wide range of disease progression, ranging from latent tuberculosis (TB) to active TB. Understanding immune factors leading to the control of the infection or disease progression is essential to identify new biomarkers and targets for host-directed therapies. Innate immunity plays an important role in inflammatory imbalance observed in active TB, among which neutrophils have both beneficial and detrimental roles. Using a macaque model developing a broad range of clinical forms of TB, we seek to understand the links between neutrophils and disease progression. We found that rapid progression to active TB leads to type I interferon signalling and neutrophil activation. In the blood, immature neutrophils were enriched when the disease progressed. In case of severe TB, Neutrophils also infiltrate a specific region of lung TB lesions rich in T lymphocytes, whereas they could modulate CD8 T cells. Our study provides new insights into the role of neutrophils in TB progression.

immunology↗

bioRxiv2025

The vaginal microbiota composition influences cervicovaginal and systemic inflammation induced by Chlamydia trachomatis infection.

BackgroundChlamydiosis, a sexually transmitted infection (STI) induced by Chlamydia trachomatis (CT), increases local inflammation (cytokine production, recruitment of immune cells such as neutrophils). Few is known on the impact of CT infection on the phenotype of cervicovaginal neutrophils. Vaginal microbiota (VM) is a key factor in the regulation of local immune responses and STI acquisition where Lactobacillus spp are associated with protection. In this study, the VM of cynomolgus macaques was enriched with Lactobacillus crispatus after local metronidazole treatment followed by repeated intravaginal inoculations of CT. VM composition, CT infection and local and systemic inflammation were monitored. ResultsFirst, we observed that metronidazole treatment induced drastic modifications of the VM by reducing the abundance of several anaerobes and increasing the number of natural Lactobacillus spp (Lactobacillus johnsonii and its prophage mainly) as well as opportunistic bacteria (Streptococcus spp and Staphylococcus spp). After CT exposure of L. crispatus treated or not animals, a non-persisting CT infection and no association between L. crispatus enrichment and a lower susceptibility to CT infection were detected. However, the production of serum specific anti-CT IgG was higher in L. crispatus treated animals. Moreover, the production of anti-CT IgG was associated with various bacterial species. An increased production of peripheral blood cytokines after CT infection was observed in untreated animals, whereas L. crispatus treated animals exhibited an increased production of cervicovaginal cytokines. Peripheral blood neutrophils were more mature and activated after CT infection/inoculation in both groups. Very few alterations of the cervicovaginal neutrophil phenotype were noticed after CT infection. Markers expressed on neutrophils were associated with bacterial species and differences were detected according to groups. ConclusionThese results suggest a better local immune response as well as a better control on systemic inflammation upon CT infection in L. crispatus treated animals compared to untreated animals. Indeed, it highlight an impact of VM composition on the local and systemic immune responses induced by CT infection. This study confirmed that VM composition can be a powerful tool to modulate local inflammation and STI susceptibility.

immunology↗

bioRxiv2023

Optimization of neuromuscular blockade protocols in cynomolgus macaques: monitoring, doses and antagonism

BackgroundNeuromuscular blocking agents (NMBAs) are a crucial component of anaesthesia and intensive care. NMBAs are a family of molecules defined by their ability to compete with acetylcholine for binding to the acetylcholine receptor at the neuromuscular junction. This functional homology relies on the presence of ammonium groups in all NMBAs that, however, display vastly different chemical structures. Among animal models, non-human primates (NHP) are an essential model for a great diversity of human disease models but remain poorly characterized for the effectiveness of the diverse NMBAs. MethodsSeven healthy male cynomolgus macaques were randomly assigned to this study. Experiments using macaques were approved by the local ethical committee (CEtEA #44). All animals were anaesthetized according to institutional guidelines, with ketamine and medetomidine, allowing IV line placement and tracheal intubation. Anaesthesia was maintained with isofluorane. Either rocuronium bromine or atracurium besylate was evaluated, with reversal with sugammadex. Monitoring was performed with two devices, TOF-Watch(R) and ToFscan(R), measuring the T4/T1 and the T4/Tref ratios, respectively. Nonparametric Mann-Whitney statistical analyses were done when indicated. ResultsNMBA monitoring required adaptation compared to humans, such as stimulus intensity and electrodes placement, to be efficient and valid in Cynomolgus macaques. When administered, both NMBAs induced deep and persistent neuro-muscular blockade at equivalent doses to clinical doses in humans. Rocuronium-induced profound neuromuscular blockade could be reverted using the cyclodextrin sugammadexs reversal agent. We report no adverse effects in these models by clinical observation, blood chemistry, or complete blood count. ConclusionThese results support the use of non-human primate models for neuromuscular blockade monitoring and testing novel NMBA or their reversal agents.

pathology↗

bioRxiv2021

Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects Macaques from infection

The SARS-CoV-2 pandemic causes an ongoing global health crisis, which requires efficient and safe vaccination programs. Here, we present synthetic SARS-CoV2 S glycoprotein-coated liposomes that resemble in size and surface structure virus-like particles. Soluble S glycoprotein trimers were stabilized by formaldehyde cross-linking and coated onto lipid vesicles (S-VLP). Immunization of cynomolgus macaques with S-VLPs induced high antibody titers and TH1 CD4+ biased T cell responses. Although antibody responses were initially dominated by RBD specificity, the third immunization boosted non-RBD antibody titers. Antibodies showed potent neutralization against the vaccine strain and the Alpha variant after two immunizations and robust neutralization of Beta and Gamma strains. Challenge of animals with SARS-CoV-2 protected all vaccinated animals by sterilizing immunity. Thus, the S-VLP approach is an efficient and safe vaccine candidate based on a proven classical approach for further development and clinical testing.

immunology↗

bioRxiv2020

Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection

The SARS-CoV-2 pandemic is continuing to disrupt personal lives, global healthcare systems and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits and cynomolgus macaques. The vaccine-induced immunity protected macaques against a high dose challenge, resulting in strongly reduced viral infection and replication in upper and lower airways. These nanoparticles are a promising vaccine candidate to curtail the SARS-CoV-2 pandemic.

immunology↗