Biology subjects

Joly, C.

Publications and source records attributed to Joly, C..

4 recordsLinked to original sources

bioRxiv2026

Rethinking human AMY1 copy number evolution in light of demographic history

Dietary change is often invoked as a major selective force in recent human evolution, with increased copy number of the salivary amylase gene (AMY1) widely cited as an adaptation to starch-rich agricultural diets. However, most evidence for this model comes from limited geographical sampling and analyses that do not fully account for shared ancestry. Here we combine newly generated droplet digital PCR estimates from 390 individuals representing 30 Sub-Saharan African populations with published copy number data from up to 1,307 individuals worldwide and re-evaluate AMY1 evolution using ancestry-aware and phylogenetically informed models. Across Africa, AMY1 copy number shows no consistent association with agriculture once population structure is accounted for. At a global scale, differences between agriculturalists and non-agriculturalists are substantially smaller than previously reported and are largely explained by shared ancestry rather than diet. Phylogenetic analyses further reveal baseline differences in AMY1 copy number between Sub-Saharan and non-Sub-Saharan populations, pointing to deep demographic processes shaping present-day variation. These results challenge the long-standing "agriculture hypothesis" and identify demographic history, rather than subsistence strategy, as the primary driver of AMY1 CN evolution worldwide.

evolutionary biology↗

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↗

bioRxiv2023

A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates

After clean drinking water, vaccination is the most impactful global health intervention. However, development of new vaccines against difficult-to-target diseases is hampered by the lack of diverse adjuvants for human use. Of particular interest, none of the currently available adjuvants induce Th17 cells. Here, we develop and test an improved liposomal adjuvant, termed CAF(R)10b, that incorporates a TLR-9 agonist. In a head-to-head study in non-human primates (NHPs), immunization with antigen adjuvanted with CAF(R)10b induced significantly increased antibody and cellular immune responses compared to previous CAF(R) adjuvants, already in clinical trials. This was not seen in the mouse model, demonstrating that adjuvant effects can be highly species specific. Importantly, intramuscular immunization of NHPs with CAF(R)10b induced robust Th17 responses that were observed in circulation half a year after vaccination. Furthermore, subsequent instillation of unadjuvanted antigen into the skin and lungs of these memory animals led to significant recall responses including transient local lung inflammation observed by Positron Emission Tomography-Computed Tomography (PET-CT), elevated antibody titers, and expanded systemic and local Th1 and Th17 responses, including >20% antigen-specific T cells in the bronchoalveolar lavage. Overall, CAF(R)10b demonstrated an adjuvant able to drive true memory antibody, Th1 and Th17 vaccine-responses across rodent and primate species, supporting its translational potential.

immunology↗

bioRxiv2021

The route of vaccine administration determines whether blood neutrophils undergo long-term phenotypic modifications

Innate immunity modulates adaptive immunity and defines the magnitude, quality, and longevity of antigen-specific T- and B- cell immune memory. Various vaccine and administration factors influence the immune response to vaccination, including the route of vaccine delivery. We studied the dynamics of innate cell responses in blood using a preclinical model of non-human primates immunized with a live attenuated vaccinia virus, Modified vaccinia virus Ankara (MVA), and mass cytometry. We previously showed that MVA induces a strong, early, and transient innate response, but also late phenotypic modifications of blood myeloid cells after two months when injected subcutaneously. Here, we show that the early innate effector cell responses and plasma inflammatory cytokine profiles differ between subcutaneous and intradermal vaccine injection. Additionally, we show that the intradermal administration fails to induce more highly activated/mature neutrophils long after immunization, in contrast to subcutaneous administration. Different batches of antibodies, staining protocols and generations of mass cytometers were used to generate the two datasets that were compared. Mass cytometry data were analyzed in parallel using the same analytical pipeline based on three successive clustering steps, including SPADE, and categorical heatmaps were compared using the Manhattan distance to measure the similarity between cell cluster phenotypes. Overall, we show that the vaccine per se is not sufficient for the late phenotypic modifications of innate myeloid cells, which are evocative of innate immune training. Its route of administration is also crucial, likely by influencing the early innate response, and systemic inflammation, and the vaccine biodistribution.

immunology↗