Sauce Publications

1. Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART

   CONCLUSIONS: Low CA-DNA after long-term suppressive ART is associated with lower CA-RNA, in concordance with other reports. Patients with low CA-RNA levels in combination with low CA-DNA and low Western Blot scores should be further investigated to characterize candidates for treatment interruption trials. Unspliced CA-RNA warrants further investigation as a marker that can be prioritized in paediatric clinical trials where the sample volume can be a significant limitation.

2. Frailty is related to serum inflammageing markers: results from the VITAL study

   Frailty describes an age-associated state in individuals with an increased vulnerability and less resilience against adverse outcomes. To score frailty, studies have employed the questionnaires, such as the SF-36 and EQ-5D-3L, or the Frailty Index, a composite score based on deficit accumulation. Furthermore, ageing of the immune system is often accompanied by a state of low-grade inflammation (inflammageing). Here, we aimed to associate 29 circulating markers of inflammageing with frailty...

3. Expression of immune checkpoint on subset of monocytes in old patients

   CONCLUSION: Our results suggest that the immune regulation which should take place post-acute stress may be affected in old individuals.

4. IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fracture

   Following acute stress such as trauma or sepsis, most of critically ill elderly patients become immunosuppressed and susceptible to secondary infections and enhanced mortality. We have developed a virus-based immunotherapy encoding human interleukin-7 (hIL-7) aiming at restoring both innate an adaptative immune homeostasis in these patients. We assessed the impact of this encoded hIL-7 on the ex vivo immune functions of T cells from PBMC of immunosenescent patients with or without hip fracture....

5. Clinical, Virological and Immunological Subphenotypes in a Cohort of Early Treated HIV-Infected Children

   CONCLUSIONS: Three HIV pediatric subphenotypes with different virological and immunological features were identified. The most favorable cluster was characterized by a higher rate of immune reconstitution and a slower disease progression, and the less favorable with more senescence and high reservoir size. In the near future therapeutic interventions for a path of a cure might be guided or supported by the different subphenotypes.

6. Primary immune responses are negatively impacted by persistent herpesvirus infections in older people: results from an observational study on healthy subjects and a vaccination trial on subjects aged more than 70 years old

   BACKGROUND: Advanced age is accompanied by a decline of immune functions, which may play a role in increased vulnerability to emerging pathogens and low efficacy of primary vaccinations in elderly people. The capacity to mount immune responses against new antigens is particularly affected in this population. However, its precise determinants are not fully understood. We aimed here at establishing the influence of persistent viral infections on the naive T-cell compartment and primary immune...

7. Mechanisms of immune aging in HIV

   Massive CD4+ T-cell depletion as well as sustained immune activation and inflammation are hallmarks of Human Immunodeficiency Virus (HIV)-1 infection. In recent years, an emerging concept draws an intriguing parallel between HIV-1 infection and aging. Indeed, many of the alterations that affect innate and adaptive immune subsets in HIV-infected individuals are reminiscent of the process of immune aging, characteristic of old age. These changes, of which the presumed cause is the systemic immune...

8. LOX-1-Expressing Immature Neutrophils Identify Critically-Ill COVID-19 Patients at Risk of Thrombotic Complications

   CONCLUSION: LOX-1-expressing ImNs may help identifying COVID-19 patients at high risk of severity and thrombosis complications.

9. 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.

10. Immune activation and chronic inflammation: Is there an additional effect of HIV in a geriatric population?

    HIV infection has become a chronic disease, with a lower mortality, but a consequent increase in age-related noninfectious comorbidities. Metabolic disorders have been linked to the effect of cART as well to the effects of immune activation and chronic inflammation. Whereas it is known that aging is intrinsically associated with hyperinflammation and immune system deterioration, the relative impact of chronic HIV infection on such inflammatory and immune activation has not yet been studied...

11. Distinct cytokine profiles associated with COVID-19 severity and mortality

    CONCLUSIONS: Distinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality according to oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.

12. Hip Fracture Leads to Transitory Immune Imprint in Older Patients

    Background: Hip fracture (HF) is common in the geriatric population and is associated with a poor vital and functional prognosis which could be impacted by immunological changes. The objective here is to decipher immune changes occurring in the 1st days following HF and determine how phenotype, function, and regulation of innate and adaptive compartments adapt during acute stress event. Methods: We included HF patients, aged over 75 years. For each patient, blood samples were taken at five...

13. Serum Tryptophan-Derived Quinolinate and Indole-3-Acetate Are Associated With Carotid Intima-Media Thickness and its Evolution in HIV-Infected Treated Adults

    CONCLUSIONS: In these highly selected HIV-positive ART-controlled males, 2 novel metabolites derived from tryptophan catabolism, indole-3-acetate and quinolinate, were associated with c-IMT and its progression.

14. Assessing T Lymphocyte Aging Using Telomere Length and Telomerase Activity Measurements in Low Cell Numbers

    As T lymphocytes proliferate and differentiate in vivo or in vitro, their functional capacity can change dramatically. In particular, extensive cell division is often associated with telomere shortening and the onset of cellular senescence, thus impacting the proliferative potential of the cells. Telomere length and integrity represent therefore key molecular markers of the status and aging of the cells. To assess these markers, we established qPCR-based methods to measure telomere length as...

15. HIV-mediated immune aging in young adults infected perinatally or during childhood

    CONCLUSION: HIV-infected young adults can present increased markers of immune activation and senescence, related to uncontrolled viral replication. This highlights the issue of noncompliance to antiretroviral therapy in patients at a young age, resulting in loss of viral control, premature immunosenescence, and potentially irreversible damage of their lymphopoietic system.

16. 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...

17. The hallmarks of CMV-specific CD8 T-cell differentiation

    Upon cytomegalovirus (CMV) infection, large T-cell responses are elicited that remain high or even increase over time, a phenomenon named memory T-cell inflation. Besides, the maintained robust T-cell response, CMV-specific T cells seem to have a distinctive phenotype, characterized by an advanced differentiation state. Here, we will review this "special" differentiation status by discussing the cellular phenotype based on the expression of CD45 isoforms, costimulatory, inhibitory and natural...

18. New Insights into Lymphocyte Differentiation and Aging from Telomere Length and Telomerase Activity Measurements

    αβ CD8^(+), γδ, and NK lymphocytes are fundamental effector cells against viruses and tumors. These cells can be divided into multiple subsets according to their phenotype. Based on progressive telomere attrition from naive to late effector memory cells, human CD8^(+) T cell subsets have been positioned along a pathway of differentiation, which is also considered as a process of lymphocyte aging or senescence. A similar categorization has not been clearly established for γδ and NK cell...

19. Aging of the immune system: From fundamental to clinical data

    Major progress in preventing, delaying or curing various pathologies normally encountered in old age results in a continuous improvement in life expectancy. However, understanding the underlying cause of the disparate comorbidities occurrence with aging remains a priority in order to propose adapted care for the older population. In one hand, aging profoundly impairs the immune system; it is characterized by many changes in haematopoiesis, adaptive and innate systems, and is associated with...

20. Elderly human hematopoietic progenitor cells express cellular senescence markers and are more susceptible to pyroptosis

    The maintenance of effective immunity over time is dependent on the capacity of hematopoietic stem cells (HSCs) to sustain the pool of immunocompetent mature cells. Decline of immune competence with old age may stem from HSC defects, including reduced self-renewal potential and impaired lymphopoiesis, as suggested in murine models. To obtain further insights into aging-related alteration of hematopoiesis, we performed a comprehensive study of blood hematopoietic progenitor cells (HPCs) from...

21. Impact of stress on aged immune system compartments: Overview from fundamental to clinical data

    Life expectancy is continuously increasing due to major progress in preventing, delaying or curing various pathologies normally encountered in old age. However, both scientific and medical advances are still required to understand underlying cause of the disparate comorbidities occurrence with aging. In one hand, aging profoundly impairs the immune system; it is characterized by many changes in haematopoiesis, adaptive and innate systems, associated with pro-inflammatory environment. In another...

22. The Oxygen Paradox, the French Paradox, and age-related diseases

    A paradox is a seemingly absurd or impossible concept, proposition, or theory that is often difficult to understand or explain, sometimes apparently self-contradictory, and yet ultimately correct or true. How is it possible, for example, that oxygen "a toxic environmental poison" could be also indispensable for life (Beckman and Ames Physiol Rev 78(2):547-81, 1998; Stadtman and Berlett Chem Res Toxicol 10(5):485-94, 1997)?: the so-called Oxygen Paradox (Davies and Ursini 1995; Davies Biochem Soc...

23. 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...

24. A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness

    Approximately 50% of individuals aged 6-49 years in the United States are infected with cytomegalovirus (CMV), with seroprevalence increasing with age, reaching 85-90% by 75-80 years according to Bate et al. (Clin Infect Dis 50 (11): 1439-1447, 2010) and Pawelec et al. (Curr Opin Immunol 24:507-511, 2012). Following primary infection, CMV establishes lifelong latency with periodic reactivation. Immunocompetent hosts experience largely asymptomatic infection, but CMV can cause serious illness in...

25. Aging of the immune system: Focus on inflammation and vaccination

    Major advances in preventing, delaying, or curing individual pathologies are responsible for an increasingly long life span in the developed parts of our planet, and indeed reaching eight to nine decades of life is nowadays extremely frequent. However, medical and sanitary advances have not prevented or delayed the underlying cause of the disparate pathologies occurring in the elderly: aging itself. The identification of the basis of the aging processes that drives the multiple pathologies and...

26. Preservation of Lymphopoietic Potential and Virus Suppressive Capacity by CD8+ T Cells in HIV-2-Infected Controllers

    Compared with HIV-1, HIV-2 infection is characterized by a larger proportion of slow or nonprogressors. A better understanding of HIV-2 pathogenesis should open new therapeutic avenues to establish control of HIV-1 replication in infected patients. In this study, we studied the production of CD8(+) T cells and their capacity for viral control in HIV-2 controllers from the French ANRS CO5 HIV-2 cohort. HIV-2 controllers display a robust capacity to support long-term renewal of the CD8(+) T cell...

27. 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...

28. Assessing immune aging in HIV-infected patients

    Many of the alterations that affect innate and adaptive immune cell compartments in HIV-infected patients are reminiscent of the process of immune aging, characteristic of old age. These alterations define the immunological age of individuals and are likely to participate to the decline of immune competence with HIV disease progression. It is therefore important to characterize these changes, which point toward the accumulation of highly differentiated immunocompetent cells, associated with...

29. Reduced Oxidative Burst by Primed Neutrophils in the Elderly Individuals Is Associated With Increased Levels of the CD16bright/CD62Ldim Immunosuppressive Subset

    The aim of our study was to analyze polymorphonuclear neutrophil (PMN) functions in elderly individuals compared with those in healthy young participants, directly in whole blood to avoid issues with data interpretation related to cell isolation procedures. Despite the presence of increased circulating levels of proinflammatory cytokines, resting PMNs from the elderly individuals were not activated as shown by normal CD62L and CD11b expression at the PMN surface and normal constitutive reactive...

30. 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...

31. Reduced naïve CD8(+) T-cell priming efficacy in elderly adults

    Aging is associated with impaired vaccine efficacy and increased susceptibility to infectious and malignant diseases. CD8(+) T-cells are key players in the immune response against pathogens and tumors. In aged mice, the dwindling naïve CD8(+) T-cell compartment is thought to compromise the induction of de novo immune responses, but no experimental evidence is yet available in humans. Here, we used an original in vitro assay based on an accelerated dendritic cell coculture system in unfractioned...

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

    No abstract

33. 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.

34. 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.

35. Vitamin D supplementation is associated with reduced immune activation levels in HIV-1-infected patients on suppressive antiretroviral therapy

    CONCLUSION: The present data support the rationale of vitamin D supplementation in the routine clinical management of HIV-1-infected patients, in order to decrease immune activation levels and possibly improve long-term survival.

36. New advances in CMV and immunosenescence

    Immunosenescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterized by impaired protective immunity and decreased efficacy of vaccines. An increasing number of immunological, clinical and epidemiological studies suggest that persistent Cytomegalovirus (CMV) infection is associated with accelerated aging of the immune system and with several age-related diseases. However, current evidence on whether and how human CMV (HCMV) infection is implicated...

37. Naive T cells: the crux of cellular immune aging?

    When encountering foreign antigens, naïve T cells become activated and differentiate into effector and memory T cells. They represent therefore the primary source to mount an immune response against pathogens or tumors. Recent evidence of both quantitative and qualitative alterations of naïve T cells has accumulated in aged mice, indicating that the successful generation of primary T cell responses from the naïve T cell pool may be compromised with old age. However, the vast majority of the data...

38. The link between CD8⁺ T-cell antigen-sensitivity and HIV-suppressive capacity depends on HLA restriction, target epitope and viral isolate

    CONCLUSIONS: Collectively, these data emphasize the central role of the TCR as a determinant of CD8⁺ T-cell efficacy and demonstrate that the complexities of antigen recognition across epitope and HLA class I boundaries can confound simple relationships between TCR engagement and HIV suppression.

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

    No abstract

40. 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...

41. 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...

42. Monitoring cellular immune markers in HIV infection: from activation to exhaustion

    PURPOSE OF REVIEW: The pathogenesis of HIV infection is highly complex and involves numerous actors of the immune system. On the one hand, our immunity has a predominant role in limiting HIV replication and the depletion of its targets, but on the other hand, the persistent infection established by the virus is associated with chronic immune activation and inflammation, potentially resulting in the progressive exhaustion of the host immune resources, and in the onset of non-AIDS-defining...

43. 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...

44. CMV and Immunosenescence: from basics to clinics

    Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates "immunosenescence". This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012....

45. 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...