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Emerging Microbes & Infections Dec 2024This review gives an overview of the protective role of CD8 T cells in SARS-CoV-2 infection. The cross-reactive responses intermediated by CD8 T cells in unexposed... (Review)
Review
This review gives an overview of the protective role of CD8 T cells in SARS-CoV-2 infection. The cross-reactive responses intermediated by CD8 T cells in unexposed cohorts are described. Additionally, the relevance of resident CD8 T cells in the upper and lower airway during infection and CD8 T-cell responses following vaccination are discussed, including recent worrisome breakthrough infections and variants of concerns (VOCs). Lastly, we explain the correlation between CD8 T cells and COVID-19 severity. This review aids in a deeper comprehension of the association between CD8 T cells and SARS-CoV-2 and broadens a vision for future exploration.
Topics: Humans; COVID-19; SARS-CoV-2; CD8-Positive T-Lymphocytes; Cross Reactions; Vaccination
PubMed: 37990907
DOI: 10.1080/22221751.2023.2287118 -
Current Rheumatology Reports Dec 2023The resident gut microbiota serves as a double-edged sword that aids the host in multiple ways to preserve a healthy equilibrium and serve as early companions and... (Review)
Review
PURPOSE OF REVIEW
The resident gut microbiota serves as a double-edged sword that aids the host in multiple ways to preserve a healthy equilibrium and serve as early companions and boosters for the gradual evolution of our immune defensive layers; nevertheless, the perturbation of the symbiotic resident intestinal communities has a profound impact on autoimmunity induction, particularly in systemic lupus erythematosus (SLE). Herein, we seek to critically evaluate the microbiome research in SLE with a focus on intestinal dysbiosis.
RECENT FINDINGS
SLE is a complex and heterogeneous disorder with self-attack due to loss of tolerance, and there is aberrant excessive immune system activation. There is mounting evidence suggesting that intestinal flora disturbances may accelerate the formation and progression of SLE, presumably through a variety of mechanisms, including intestinal barrier dysfunction and leaky gut, molecular mimicry, bystander activation, epitope spreading, gender bias, and biofilms. Gut microbiome plays a critical role in SLE pathogenesis, and additional studies are warranted to properly define the impact of gut microbiome in SLE, which can eventually lead to new and potentially safer management approaches for this debilitating disease.
Topics: Humans; Female; Male; Gastrointestinal Microbiome; Dysbiosis; Sexism; Lupus Erythematosus, Systemic; Autoimmunity
PubMed: 37737528
DOI: 10.1007/s11926-023-01115-8 -
Nature Medicine Oct 2023The main barrier to HIV cure is a persistent reservoir of latently infected CD4 T cells harboring replication-competent provirus that fuels rebound viremia upon...
The main barrier to HIV cure is a persistent reservoir of latently infected CD4 T cells harboring replication-competent provirus that fuels rebound viremia upon antiretroviral therapy (ART) interruption. A leading approach to target this reservoir involves agents that reactivate latent HIV proviruses followed by direct clearance of cells expressing induced viral antigens by immune effector cells and immunotherapeutics. We previously showed that AZD5582, an antagonist of inhibitor of apoptosis proteins and mimetic of the second mitochondrial-derived activator of caspases (IAPi/SMACm), induces systemic reversal of HIV/SIV latency but with no reduction in size of the viral reservoir. In this study, we investigated the effects of AZD5582 in combination with four SIV Env-specific Rhesus monoclonal antibodies (RhmAbs) ± N-803 (an IL-15 superagonist) in SIV-infected, ART-suppressed rhesus macaques. Here we confirm the efficacy of AZD5582 in inducing SIV reactivation, demonstrate enhancement of latency reversal when AZD5582 is used in combination with N-803 and show a reduction in total and replication-competent SIV-DNA in lymph-node-derived CD4 T cells in macaques treated with AZD5582 + RhmAbs. Further exploration of this therapeutic approach may contribute to the goal of achieving an HIV cure.
Topics: Animals; HIV Infections; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Macaca mulatta; Anti-Retroviral Agents; Virus Latency; Virus Replication; HIV-1; Antibodies; Lymph Nodes; CD4-Positive T-Lymphocytes; Viral Load
PubMed: 37783968
DOI: 10.1038/s41591-023-02570-7 -
Nephrology (Carlton, Vic.) Jul 2023Autoinflammatory diseases (AIDs) are mostly caused by dysfunctions in single genes encoding for proteins with a prominent role in the regulation of innate immunity, such... (Review)
Review
Autoinflammatory diseases (AIDs) are mostly caused by dysfunctions in single genes encoding for proteins with a prominent role in the regulation of innate immunity, such as complement factors, inflammasome components, tumour necrosis factor (TNF)-α, and proteins belonging to type I-interferon (IFN) signalling pathways. Due to the deposition of amyloid A (AA) fibrils in the glomeruli, unprovoked inflammation in AIDs frequently affects renal health. In fact, secondary AA amyloidosis is the most common form of amyloidosis in children. It is caused by the extracellular deposition of fibrillar low-molecular weight protein subunits resulting from the degradation and accumulation of serum amyloid A (SAA) in numerous tissues and organs, primarily the kidneys. The molecular mechanisms underlying AA amyloidosis in AIDs are the elevated levels of SAA, produced by the liver in response to pro-inflammatory cytokines, and a genetic predisposition due to specific SAA isoforms. Despite the prevalence of amyloid kidney disease, non-amyloid kidney diseases may also be responsible for chronic renal damage in children with AIDs, albeit with distinct characteristics. Glomerular damage can result in various forms of glomerulonephritis with distinct histologic characteristics and a different underlying pathophysiology. This review aims to describe the potential renal implications in patients with inflammasomopathies, type-I interferonopathies, and other rare AIDs in an effort to improve the clinical course and quality of life in paediatric patients with renal involvement.
Topics: Humans; Child; Quality of Life; Amyloidosis; Inflammation; Serum Amyloid A Protein; Hereditary Autoinflammatory Diseases
PubMed: 37142240
DOI: 10.1111/nep.14166 -
JHEP Reports : Innovation in Hepatology Aug 2023Prevention of mother-to-child transmission of hepatitis B virus (HBV) infection is a cornerstone of efforts to support progress towards elimination of viral hepatitis.... (Review)
Review
Prevention of mother-to-child transmission of hepatitis B virus (HBV) infection is a cornerstone of efforts to support progress towards elimination of viral hepatitis. Current guidelines recommend maternal screening, antiviral therapy during the third trimester of high-risk pregnancies, universal and timely HBV birth dose vaccination, and post-exposure prophylaxis with hepatitis B immunoglobulin for selected neonates. However, serological and molecular diagnostic testing, treatment and HBV vaccination are not consistently deployed, particularly in many high endemicity settings, and models predict that global targets for reduction in paediatric incidence will not be met by 2030. In this article, we briefly summarise the evidence for current practice and use this as a basis to discuss areas in which prevention of mother-to-child transmission can potentially be enhanced. By reducing health inequities, enhancing pragmatic use of resources, filling data gaps, developing advocacy and education, and seeking consistent investment from multilateral agencies, significant advances can be made to further reduce vertical transmission events, with wide health, societal and economic benefits.
PubMed: 37554925
DOI: 10.1016/j.jhepr.2023.100777 -
Immunity Jul 2023Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5) can cure HIV, yet mechanisms remain speculative. To...
Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5) can cure HIV, yet mechanisms remain speculative. To define how alloHSCT mediates HIV cure, we performed MHC-matched alloHSCT in SIV, anti-retroviral therapy (ART)-suppressed Mauritian cynomolgus macaques (MCMs) and demonstrated that allogeneic immunity was the major driver of reservoir clearance, occurring first in peripheral blood, then peripheral lymph nodes, and finally in mesenteric lymph nodes draining the gastrointestinal tract. While allogeneic immunity could extirpate the latent viral reservoir and did so in two alloHSCT-recipient MCMs that remained aviremic >2.5 years after stopping ART, in other cases, it was insufficient without protection of engrafting cells afforded by CCR5-deficiency, as CCR5-tropic virus spread to donor CD4 T cells despite full ART suppression. These data demonstrate the individual contributions of allogeneic immunity and CCR5 deficiency to HIV cure and support defining targets of alloimmunity for curative strategies independent of HSCT.
Topics: Animals; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; HIV Infections; Macaca fascicularis; Hematopoietic Stem Cell Transplantation; Viral Load
PubMed: 37236188
DOI: 10.1016/j.immuni.2023.04.019 -
Clinical Infectious Diseases : An... Dec 2023While the coronavirus disease 2019 (COVID-19) pandemic continues to present global challenges, sufficient time has passed to reflect on lessons learned and use those...
While the coronavirus disease 2019 (COVID-19) pandemic continues to present global challenges, sufficient time has passed to reflect on lessons learned and use those insights to inform policy and approaches to prepare for the next pandemic. In May 2022, the Duke Clinical Research Institute convened a think tank with thought leaders from academia, clinical practice, the pharmaceutical industry, patient advocacy, the National Institutes of Health, the US Food and Drug Administration, and the Centers for Disease Control and Prevention to share, firsthand, expert knowledge of the insights gained from the COVID-19 pandemic and how this acquired knowledge can help inform the next pandemic response. The think tank focused on pandemic preparedness, therapeutics, vaccines, and challenges related to clinical trial design and scale-up during the early phase of a pandemic. Based on the multi-faceted discussions, we outline 10 key steps to an improved and equitable pandemic response.
Topics: United States; Humans; COVID-19; Pandemics; National Institutes of Health (U.S.)
PubMed: 37435958
DOI: 10.1093/cid/ciad418 -
The American Journal of Clinical... Oct 2023Body composition assessment aids evaluation of energy stores and the impact of diseases and interventions on child growth. Current United States pediatric reference... (Observational Study)
Observational Study
BACKGROUND
Body composition assessment aids evaluation of energy stores and the impact of diseases and interventions on child growth. Current United States pediatric reference ranges from the National Health and Nutrition Examination Survey (NHANES) include 20% of children with obesity, body mass index of ≥95th percentile.
OBJECTIVES
This study aimed to develop dual energy X-ray absorptiometry (DXA) based reference ranges in a diverse cohort with low-obesity prevalence from the Bone Mineral Density in Childhood Study (BMDCS).
METHODS
This is a secondary analysis of a longitudinal, prospective, observational cohort. Healthy children (height and BMI within 3rd to 97th percentiles, ages 5-19 y at enrollment), from 5 United States centers were measured annually for ≤7 visits. Whole body scans were acquired using Hologic scanners. A subsample underwent repeat measurements to determine precision. We generated reference ranges for appendicular and total lean soft tissue mass index (LSTM Index), fat mass index (FMI), and other body composition measures. Resulting curves were compared to NHANES and across subgroups. Sex and age-specific equations were developed to adjust body composition Z-scores for height Z score.
RESULTS
We obtained 9846 scans of 2011 participants (51% female, 22% Black, 17% Hispanic, 48% White, 7% Asian/Pacific Islander, and 6% with obesity). Precision (percent coefficient of variation) ranged from 0.7% to 1.96%. Median and-2 standard deviation curves for BMDCS and NHANES were similar, but NHANES +2 standard deviation LSTM Index and FMI curves were distinctly greater than the respective BMDCS curves. Subgroup differences were more extreme for appendicular LSTM Index-Z (mean ± SD: Asian -0.52 ± 0.93 compared with Black 0.77 ± 0.87) than for FMI-Z (Hispanic 0.29 ± 0.98 compared with Black -0.14 ± 1.1) and were smaller for Z-scores adjusted for height Z-score.
CONCLUSIONS
These reference ranges add to sparse normative data regarding body composition in children and adolescents and are based on a cohort with an obesity prevalence similar to current BMI charts. Awareness of subgroup differences aids in interpreting results.
Topics: Adolescent; Humans; Female; Child; United States; Male; Absorptiometry, Photon; Bone Density; Nutrition Surveys; Reference Values; Prospective Studies; Body Composition; Obesity; Body Mass Index
PubMed: 37598746
DOI: 10.1016/j.ajcnut.2023.08.006 -
Journal of Medical Imaging and... Nov 2023Histiocytoses are rare multi-system disorders marked by abnormal histiocyte cell proliferation, affecting children with diverse clinical presentations. Classified into...
Histiocytoses are rare multi-system disorders marked by abnormal histiocyte cell proliferation, affecting children with diverse clinical presentations. Classified into five groups in 2016, including Langerhans-related (L), cutaneous (C), malignant (M), Rosai-Dorfman disease (R) and haemophagocytic lymphohistiocytosis (H), newer entities such as ALK-positive histiocytosis have also emerged, heralding the era of molecular (sub)classification. Common entities include Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD) and haemophagocytic lymphohistiocytosis (HLH). This pictorial essay aids radiologists in recognising and differentiating paediatric histiocytoses based on unique neuroimaging features.
PubMed: 37964685
DOI: 10.1111/1754-9485.13602 -
The Journal of Infectious Diseases Aug 2023Immune mechanisms that modulate human immunodeficiency virus-1 (HIV-1) reservoir size in neonates are poorly understood. Using samples from neonates who initiated...
Immune mechanisms that modulate human immunodeficiency virus-1 (HIV-1) reservoir size in neonates are poorly understood. Using samples from neonates who initiated antiretroviral therapy shortly after birth, we demonstrate that interleukin-8-secreting CD4 T cells, which are selectively expanded in early infancy, are more resistant to HIV-1 infection and inversely correlated with the frequency of intact proviruses at birth. Moreover, newborns with HIV-1 infection displayed a distinct B-cell profile at birth, with reduction of memory B cells and expansion of plasmablasts and transitional B cells; however, B-cell immune perturbations were unrelated to HIV-1 reservoir size and normalized after initiation of antiretroviral therapy. Clinical Trials Registration. NCT02369406.
Topics: Humans; Infant, Newborn; HIV-1; Anti-Retroviral Agents; HIV Infections; Proviruses; CD4-Positive T-Lymphocytes; Viral Load
PubMed: 37201510
DOI: 10.1093/infdis/jiad173