My Publications

1. Predictive gene expression signature diagnoses neonatal sepsis before clinical presentation

   BACKGROUND: Neonatal sepsis is a deadly disease with non-specific clinical signs, delaying diagnosis and treatment. There remains a need for early biomarkers to facilitate timely intervention. Our objective was to identify neonatal sepsis gene expression biomarkers that could predict sepsis at birth, prior to clinical presentation.

2. Clinical Staphylococcus aureus inhibits human T-cell activity through interaction with the PD-1 receptor

   Therapies that target and aid the host immune defense to repel cancer cells or invading pathogens are rapidly emerging. Antibiotic resistance is among the largest threats to human health globally. Staphylococcus aureus (S. aureus) is the most common bacterial infection, and it poses a challenge to the healthcare system due to its significant ability to develop resistance toward current available therapies. In long-term infections, S. aureus further adapt to avoid clearance by the host immune...

3. Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients

   CONCLUSION: We propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.

4. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

   Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522...

5. Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants

   Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations may diminish vaccine-induced protective immune responses, particularly as antibody titers wane over time. Here, we assess the effect of SARS-CoV-2 variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.429 (Epsilon), B.1.526 (Iota), and B.1.617.2 (Delta) on binding, neutralizing, and angiotensin-converting enzyme 2 (ACE2)–competing antibodies elicited by the messenger RNA (mRNA) vaccine mRNA-1273 over 7 months....

6. Perturbed Microbiota/Immune Homeostasis in Multiple Sclerosis

   CONCLUSIONS: Gut and systemic microbiota/immune homeostasis are perturbed in MS. Our results argue that defective IgA responses in MS are linked to a breakdown of systemic tolerance to gut microbiota leading to an enhanced triggering of systemic IgG immunity against gut commensals occurring early in MS.

7. Systemic anti-commensal response to fungi analyzed by flow cytometry is related to gut mycobiome ecology

   CONCLUSIONS: Fungi-Flow allows an easy and reliable measure of personalized humoral responses against commensal fungi. Combining sequencing technology with our novel Fungi-Flow immunological method, we propose that there are at least two defined ecosystems in the human gut mycobiome associated with systemic humoral responses. Fungi-Flow opens new opportunities to improve our knowledge about the impact of mycobiota in humoral anti-commensal immunity and homeostasis. Video Abstract.

8. BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis

   Death from sepsis in the neonatal period remains a serious threat for millions. Within 3 days of administration, bacille Calmette-Guérin (BCG) vaccination can reduce mortality from neonatal sepsis in human newborns, but the underlying mechanism for this rapid protection is unknown. We found that BCG was also protective in a mouse model of neonatal polymicrobial sepsis, where it induced granulocyte colony-stimulating factor (G-CSF) within hours of administration. This was necessary and sufficient...

9. Correction: Human IgA bind a diverse array of commensal bacteria

   No abstract

10. Human IgA binds a diverse array of commensal bacteria

    In humans, several grams of IgA are secreted every day in the intestinal lumen. While only one IgA isotype exists in mice, humans secrete IgA1 and IgA2, whose respective relations with the microbiota remain elusive. We compared the binding patterns of both polyclonal IgA subclasses to commensals and glycan arrays and determined the reactivity profile of native human monoclonal IgA antibodies. While most commensals are dually targeted by IgA1 and IgA2 in the small intestine, IgA1+IgA2+ and...

11. Phenotypic and Functional Differences between Human Herpesvirus 6- and Human Cytomegalovirus-Specific T Cells

    Human herpesvirus 6 (HHV-6) infects >90% of the population and establishes a latent infection with asymptomatic episodes of reactivation. However, HHV-6 reactivation is associated with morbidity and sometimes mortality in immunocompromised patients. To date, control of the virus in healthy virus carriers and the failure to control it in patients with disease remain poorly understood. In particular, knowledge of HHV-6-specific T-cell responses is limited. Here, we characterized HHV-6A- and...

12. Tear staining in finisher pigs and its relation to age, growth, sex and potential pen level stressors

    Tear staining (TS) in the pig has been related to different stressors and may be a useful tool for assessing animal welfare on farm. The aim of the current study was to investigate TS across the finisher period and its possible relation to age, growth, sex and experimentally induced stressors. The study included 80 finisher pens divided between three batches. Within each batch, the pens either included pigs with docked or undocked tails, had straw provided (150 g/pig/day) or not and had a low...

13. Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

    CONCLUSION: Secretory IgA and systemic IgG converge to target gut microbiota at the cellular level. SIgAd-associated inflammation is inversely correlated with systemic anticommensal IgG responses, which might serve as a second line of defense. We speculate that patients with SIgAd could benefit from oral IgA supplementation. Our data also suggest that intravenous immunoglobulin preparations can be supplemented with IgG from IgA-deficient patient pools to offer better protection against gut...

14. Immune/microbial interface perturbation in human IgA deficiency

    In a recently published article we report the metagenomic analysis of human gut microbiomes evolved in the absence of immunoglobulin A (IgA). We show that human IgA deficiency is not associated with massive quantitative perturbations of gut microbial ecology. While our study underlines a rather expected pathobiont expansion, we at the same time highlight a less expected depletion in some typically beneficial symbionts. We also show that IgM partially supply IgA deficiency, explaining the...

15. Microbial ecology perturbation in human IgA deficiency

    Paradoxically, loss of immunoglobulin A (IgA), one of the most abundant antibodies, does not irrevocably lead to severe infections in humans but rather is associated with relatively mild respiratory infections, atopy, and autoimmunity. IgA might therefore also play covert roles, not uniquely associated with control of pathogens. We show that human IgA deficiency is not associated with massive quantitative perturbations of gut microbial ecology. Metagenomic analysis highlights an expected...

16. Elevated Neopterin Levels Predict Early Death in Older Hip-fracture Patients

    Our society faces a major challenge concerning management of the health and socio-economic burden caused by acute physical stress in the older population (+75years). In particular, hip-fracture surgery (HFS) represents a major health care preoccupation, affecting 1.6 million patients worldwide, resulting in a significant drop in life quality and autonomy. The trauma is associated with 20-30% one-year mortality in the elderly. In the present study, we aim to identify factors, which influence...

17. La génétique de l’hôte influe sur les écosystèmes microbiens par l’intermédiaire du système immunitaire de l’hôte

    Genetic evolution of multicellular organisms occurred as a response to environmental challenges, in particular competition for nutrients, climatic change, physical and chemical stressors and pathogens. However organism fitness depends on both the efficiency of its defences and its capacities for benefiting from its symbiotic organisms. Indeed microbes not only engender pathogenies, but enable efficient uptake of host non-self biodegradable nutriments. Furthermore, microbes play an important role...

18. Triggering of TLR-3, -4, NOD2, and DC-SIGN reduces viral replication and increases T-cell activation capacity of HIV-infected human dendritic cells

    A variety of signals influence the capacity of dendritic cells (DCs) to mount potent antiviral cytotoxic T-cell (CTL) responses. In particular, innate immune sensing by pathogen recognition receptors, such as TLR and C-type lectines, influences DC biology and affects their susceptibility to HIV infection. Yet, whether the combined effects of PPRs triggering and HIV infection influence HIV-specific (HS) CTL responses remain enigmatic. Here, we dissect the impact of innate immune sensing by...

19. Host genetics affect microbial ecosystems via host immunity

    PURPOSE OF REVIEW: Genetic evolution of multicellular organisms has occurred in response to environmental challenges, including competition for nutrients, climate change, physical and chemical stressors, and pathogens. However, fitness of an organism is dependent not only on defense efficacy, but also on the ability to take advantage of symbiotic organisms. Indeed, microbes not only encompass pathogenicity, but also enable efficient nutrient uptake from diets nondegradable by the host itself....

20. Analysis of bacterial-surface-specific antibodies in body fluids using bacterial flow cytometry

    Antibacterial antibody responses that target surfaces of live bacteria or secreted toxins are likely to be relevant in controlling bacterial pathogenesis. The ability to specifically quantify bacterial-surface-binding antibodies is therefore highly attractive as a quantitative correlate of immune protection. Here, binding of antibodies from various body fluids to pure-cultured live bacteria is made visible with fluorophore-conjugated secondary antibodies and measured by flow cytometry. We...

21. HIV-specific Th2 and Th17 responses predict HIV vaccine protection efficacy

    Understanding the factors that delineate the efficacy of T-cell responses towards pathogens is crucial for our ability to develop potent therapies and vaccines against infectious diseases, such as HIV. Here we show that a recently developed analytical tool, the polyfunctionality index (PI), not only enables prediction of protection after vaccination against HIV, but also allows identification of the immunological pathways involved. Our data suggest that induction of a synergistic network of...

22. Coordinated expansion of both memory T cells and NK cells in response to CMV infection in humans

    NK cells are key players in the fight against persistent viruses. Human cytomegalovirus (HCMV) infection is associated with the presence of a population of CD16(+) CD56(dim) NKG2C(+) NK cells in both acutely and latently infected individuals. Here, we studied the nature of these terminally differentiated NK cells in different human populations infected with HCMV: healthy donors stratified by age, thymectomized individuals, pregnant women suffering from primary CMV infection, and lung transplant...

23. Priming of Qualitatively Superior Human Effector CD8+ T Cells Using TLR8 Ligand Combined with FLT3 Ligand

    The quality of Ag-specific CD8(+) T cell responses is central to immune efficacy in infectious and malignant settings. Inducing effector CD8(+) T cells with potent functional properties is therefore a priority in the field of immunotherapy. However, the optimal assessment of new treatment strategies in humans is limited by currently available testing platforms. In this study, we introduce an original model of in vitro CD8(+) T cell priming, based on an accelerated dendritic cell coculture...

24. Correction: Pathogen-Specific T Cell Polyfunctionality Is a Correlate of T Cell Efficacy and Immune Protection

    No abstract

25. Ultraviolet light converts propranolol, a nonselective β-blocker and potential lupus-inducing drug, into a proinflammatory AhR ligand

    UV light and some medications are known to trigger lupus erythematosus (LE). A common mechanism underlying the immunopathologic effect, resulting from exposure to these two seemingly unrelated factors, remains unknown. The aryl hydrocarbon receptor (AhR) plays a key role in the regulation of IL-22 production in humans and can be activated by both xenobiotics and naturally occurring photoproducts. A significant expansion of Th17 and Th22 cells was observed in the peripheral blood of active...

26. Comment on "Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients"

    No abstract

27. Pathogen-Specific T Cell Polyfunctionality Is a Correlate of T Cell Efficacy and Immune Protection

    CONCLUSIONS: Our study presents a generalizable methodology to objectively evaluate the impact of polyfunctionality on T cell efficacy. We show that T cell polyfunctionality is a superior correlate of T cell efficacy both in vitro and in vivo as compared with response size. Therefore, future immunotherapies should aim to increase T cell polyfunctionality.

28. Quality control of microbiota metagenomics by k-mer analysis

    CONCLUSIONS: We propose that k-mer analysis of raw metagenome sequence reads should be implemented as a first quality assessment prior to more extensive bioinformatics analysis, such as sequence filtering and gene mapping. With the rising demand for metagenomic analysis of microbiota it is crucial to provide tools for rapid and efficient decision making. This will eventually lead to a faster turn-around time, improved analytical quality including sample quality metrics and a significant cost...

29. Increased carotid intima-media thickness is not associated with T-cell activation nor with cytomegalovirus in HIV-infected never-smoker patients

    CONCLUSION: In HIV-infected individuals at low cardiovascular disease risk, our data show that the increased risk of carotid atherosclerosis is not associated with immunological markers described to be associated with HIV disease progression.

30. Functional Exhaustion Limits CD4+ and CD8+ T-Cell Responses to Congenital Cytomegalovirus Infection

    CONCLUSIONS: Functional exhaustion limits effector CD4(+) and CD8(+) T-lymphocyte responses to CMV during fetal life.

31. Epitope specificity delimits the functional capabilities of vaccine-induced CD8 T cell populations

    Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2K(d) epitope elicited high-avidity CD8 T cell populations with...

32. Single-cell analysis of innate cytokine responses to pattern recognition receptor stimulation in children across four continents

    Innate immunity instructs adaptive immunity, and suppression of innate immunity is associated with an increased risk for infection. We showed previously that whole-blood cellular components from a cohort of South African children secreted significantly lower levels of most cytokines following stimulation of pattern recognition receptors compared with whole blood from cohorts of Ecuadorian, Belgian, or Canadian children. To begin dissecting the responsible molecular mechanisms, we set out to...

33. Influence of PD-1 on the immunological synapse: a facet of immune regulation ?

    No abstract

34. Differential impact of age and cytomegalovirus infection on the γδ T cell compartment

    γδ T cells represent a subset of unconventional T lymphocytes that are known for their reactivity against different pathogens and considered as intermediate mediators between adaptive and innate immunity. We provide in this paper further insights underlying the changes that affect the γδ T cell compartment with advanced age in humans. We show that both aging and CMV infection impact independently on the γδ T cell compartment. Most γδ T cells are significantly affected by age and present a...

35. CMV driven CD8(+) T-cell activation is associated with acute rejection in lung transplantation

    Lung transplantation is the definitive treatment for terminal respiratory disease, but the associated mortality rate is high. Acute rejection of the transplanted lung is a key determinant of adverse prognosis. Furthermore, an epidemiological relationship has been established between the occurrence of acute lung rejection and cytomegalovirus infection. However, the reasons for this association remain unclear. Here, we performed a longitudinal characterization of CMV-specific T-cell responses and...

36. Lymphopenia-driven homeostatic regulation of naive T cells in elderly and thymectomized young adults

    Reduced thymopoiesis and continuous mobilization of naive T cells into the effector-memory pool can lead to severe alterations of the naive T cell compartment. However, maintenance of the naive T cell population is essential to mount effective immune responses. Evidence of homeostatic regulation of naive T cells is currently debated in animal models. In humans, the situation remains unresolved, in particular with advanced age. In this study, we analyzed the CD4(+) and CD8(+) naive T cell...

37. Evaluating cellular polyfunctionality with a novel polyfunctionality index

    Functional evaluation of naturally occurring or vaccination-induced T cell responses in mice, men and monkeys has in recent years advanced from single-parameter (e.g. IFN-γ-secretion) to much more complex multidimensional measurements. Co-secretion of multiple functional molecules (such as cytokines and chemokines) at the single-cell level is now measurable due primarily to major advances in multiparametric flow cytometry. The very extensive and complex datasets generated by this technology...

38. The Relapsing Polychondritis Disease Activity Index: development of a disease activity score for relapsing polychondritis

    CONCLUSION: We have developed the first consensus scoring system to measure disease activity in relapsing polychondritis (see www.RPDAI.org for online scoring). This tool will be valuable for improving the care of patients with this rare disease.

39. Activated and resting regulatory T cell exhaustion concurs with high levels of interleukin-22 expression in systemic sclerosis lesions

    CONCLUSION: SSc pathogenesis does not appear to be linked to IL-17-, but rather to IL-22-producing cells with skin-homing potential and a concomitant quantitative Treg defect. Active and diffuse forms of the disease are associated with a FoxP3 signature. Altogether, our data depict a status of regulatory/pro-inflammatory T cell imbalance in SSc.

40. Cytokine profiles in sepsis have limited relevance for stratifying patients in the emergency department: a prospective observational study

    CONCLUSIONS: Previous non-multiparametric studies might have reached inappropriate conclusions. Indeed, well-defined clinical conditions do not translate into particular cytokine profiles. Additional and larger trials are now required to validate the limited interest of expensive multiplex cytokine profiling for staging septic patients.