Introduction: C-type lectin receptor (CLR) agonists emerged as superior inducers of primary B cell responses in early life compared with Toll-like receptor (TLR) agonists, while both types of adjuvants are potent in adults.
Methods: Here, we explored the mechanisms accounting for the differences in neonatal adjuvanticity between a CLR-based (CAF01) and a TLR4-based (GLA-SE) adjuvant administered with influenza hemagglutinin (HA) in neonatal mice, by using transcriptomics and systems biology analyses.
Results: On day 7 after immunization, HA/CAF01 increased IL6 and IL21 levels in the draining lymph nodes, while HA/GLA-SE increased IL10.
The adaptive immune response is under circadian control, yet, why adaptive immune reactions continue to exhibit circadian changes over long periods of time is unknown. Using a combination of experimental and mathematical modeling approaches, we show here that dendritic cells migrate from the skin to the draining lymph node in a time-of-day-dependent manner, which provides an enhanced likelihood for functional interactions with T cells. Rhythmic expression of TNF in the draining lymph node enhances BMAL1-controlled ICAM-1 expression in high endothelial venules, resulting in lymphocyte infiltration and lymph node expansion.
View Article and Find Full Text PDFSARS-CoV-2 infection in children is less severe than it is in adults. We perform a longitudinal analysis of the early innate responses in children and adults with mild infection within household clusters. Children display fewer symptoms than adults do, despite similar initial viral load, and mount a robust anti-viral immune signature typical of the SARS-CoV-2 infection and characterized by early interferon gene responses; increases in cytokines, such as CXCL10 and GM-CSF; and changes in blood cell numbers.
View Article and Find Full Text PDFBackground: SARS-CoV-2 infection leads to high viral loads in the upper respiratory tract that may be determinant in virus dissemination. The extent of intranasal antiviral response in relation to symptoms is unknown. Understanding how local innate responses control virus is key in the development of therapeutic approaches.
View Article and Find Full Text PDFThe rVSV-ZEBOV Ebolavirus vaccine confers protection within days after immunization, suggesting the contribution of innate immune responses. We report modulation of rVSV-ZEBOV vaccinee blood CD56 NK cell numbers, NKG2D or NKp30 surface receptor expression, Killer Immunoglobulin-like Receptor (KIR) cell percentages and NK-cell-related genes on day 1 post immunization. Inverse correlations existed between the concentration of several plasma cytokines and inhibitory KIR CD56 or cytokine-responsive CD56 NK cells.
View Article and Find Full Text PDFT follicular helper (T) cells have emerged as a critical limiting factor for controlling the magnitude of neonatal germinal center (GC) reactions and primary vaccine antibody responses. We compared the functional attributes of neonatal and adult T cells at the transcriptomic level and demonstrated that the T cell program is well-initiated in neonates although the T gene-expression pattern (i.e.
View Article and Find Full Text PDFMaternal antibodies (MatAbs) protect offspring from infections but limit their responses to vaccination. The mechanisms of this inhibition are still debated. Using murine early-life immunization models mimicking the condition prevailing in humans, we observed the induction of CD4-T, T follicular helper, and germinal center (GC) B cell responses even when early-life antibody responses were abrogated by MatAbs.
View Article and Find Full Text PDFDendritic cells (DCs) that drain the gut and skin are known to favor the establishment of T cell populations that home to the original site of DC-antigen (Ag) encounter by providing "imprinting" signals to T cells in the lymph node (LN). To study the induction of lung T cell-trafficking, we used a protein-adjuvant murine intranasal and intramuscular immunization model to compare -activated Ag DCs in the lung and muscle-draining LNs. Higher frequencies of Ag CD11b DCs were observed in lung-draining mediastinal LNs (MedLN) compared to muscle-draining inguinal LNs (ILN).
View Article and Find Full Text PDFNeonates and infants are more vulnerable to infections and show reduced responses to vaccination. Consequently, repeated immunizations are required to induce protection and early life vaccines against major pathogens such as influenza are yet unavailable. Formulating antigens with potent adjuvants, including immunostimulators and delivery systems, is a demonstrated approach to enhance vaccine efficacy.
View Article and Find Full Text PDFMyeloid-derived suppressor cells (MDSCs) are major regulators of T cell responses in several pathological conditions. Whether MDSCs increase and influence T cell responses in temporary inflammation, such as after vaccine administration, is unknown. Using the rhesus macaque model, which is critical for late-stage vaccine testing, we demonstrate that monocytic (M)-MDSCs and polymorphonuclear (PMN)-MDSCs can be detected using several of the markers used in humans.
View Article and Find Full Text PDFNeutrophils are critical cells of the innate immune system and rapidly respond to tissue injury and infection. Increasing evidence also indicates that neutrophils have versatile functions in contributing to adaptive immunity by internalizing and transporting antigen and influencing antigen-specific responses. Here, we demonstrate that freshly isolated human neutrophils can function as antigen-presenting cells (APCs) to memory CD4 T cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2013
Vaccines are the most effective agents to control infections. In addition to the pathogen antigens, vaccines contain adjuvants that are used to enhance protective immune responses. However, the molecular mechanism of action of most adjuvants is ill-known, and a better understanding of adjuvanticity is needed to develop improved adjuvants based on molecular targets that further enhance vaccine efficacy.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2013
The venom of the snake Bothrops asper causes muscle necrosis, pain and inflammation. This venom contains myotoxins which cause an increase in intracellular Ca(2+) concentration and release of K(+) and ATP from myotubes. ATP is a key danger molecule that triggers a variety of reactions, including activation of the innate immune response.
View Article and Find Full Text PDFBackground: Low temperature plasmas have been proposed in medicine as agents for tissue disinfection and have received increasing attention due to the frequency of bacterial resistance to antibiotics. This study explored whether atmospheric-pressure cold plasma (APCP) generated by a new portable device that ionizes a flow of helium gas can inactivate ocular pathogens without causing significant tissue damage.
Methodology/principal Findings: We tested the APCP effects on cultured Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Candida albicans, Aspergillus fumigatus and Herpes simplex virus-1, ocular cells (conjunctival fibroblasts and keratocytes) and ex-vivo corneas.
Cardiovasc Ultrasound
October 2009
Background: Transthoracic echocardiography left ventricular wall thickness is often increased in master athletes and it results by intense physical training. Left Ventricular Hypertrophy can also be due to a constant pressure overload. Conventional Pulsed Wave (PW) Doppler analysis of diastolic function sometimes fails to distinguish physiological from pathological LVH.
View Article and Find Full Text PDFAims: Longitudinal peak systolic strain (LPSS) quantifies regional and global heart function. Few data are available on left ventricle (LV) performance in young athletes with bicuspid aortic valve (BAV), where a pattern of mild aortic insufficiency is relatively frequent, and the ejection fraction (EF) is often normal for a long time. We report the measurement of LV strain in young BAV athletes.
View Article and Find Full Text PDFBackground: Ultrasound speckle tracking from grey scale images allows the assessment of regional strain derived from 2D regardless of angle intonation, and it is highly reproducible. The study aimed to evaluate regional left ventricular functional reserve in elite soccer players.
Methods: 50 subjects (25 elite athletes and 25 sedentary controls), aged 26 +/- 3.
Cardiovasc Ultrasound
February 2007
Background: Myocardial contractility can be investigated using longitudinal peak strain. It can be calculated using the Doppler-derived TDI method and the non-Doppler method based on tissue tracking on B-mode images. Both are validated and show good reproducibility, but no comparative analysis of their results has yet been conducted.
View Article and Find Full Text PDFBackground: The number of competitive master athletes (MA, over 40 years) has been rising. Since the incidence of coronary artery disease (CAD) is increasing in this population, cardiovascular pre-participation screening, including a maximum exercise test, is recommended. In this context the addition of contrast to echo could be useful because wall thickening and motion are better markers of myocardial function when the whole endocardial border (EB) is visible.
View Article and Find Full Text PDFPurpose: The aim of this cross-sectional study was to determine whether there is a correlation between left ventricular hypertrophy (LVH) and angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism in adolescent athletes.
Methods: Seventy-five competitive soccer players (aged 15 +/- 1.2 yr) and 52 untrained control subjects (aged 15 +/- 1.
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