Publications by authors named "Mathieu Barrier"
Asthma is a chronic lung disease with persistent airway inflammation, bronchial hyper-reactivity, mucus overproduction, and airway remodeling. Antagonizing T2 responses by triggering the immune system with microbial components such as Toll-like receptors (TLRs) has been suggested as a therapeutic concept for allergic asthma. The aim of this study was to evaluate the effect of a TLR2/6 agonist, FSL-1 (Pam2CGDPKHPKSF), administered by intranasal instillation after an allergic airway reaction was established in the ovalbumin (OVA) mouse model and to analyze the role of natural killer (NK) cells in this effect.
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- Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) are neurodegenerative diseases characterized by tau pathology, where AD leads to cognitive decline and PSP affects movement and balance; Progranulin (PGRN) is relevant to both conditions and can be targeted by AZP2006, a synthetic compound aimed at stabilizing PGRN and reducing tau aggregation.
- A phase 1 clinical study evaluated AZP2006's safety, tolerability, and pharmacokinetics involving healthy male volunteers receiving various doses; no severe adverse events occurred, and any minor side effects were temporary.
- AZP2006 was quickly absorbed and had a favorable safety profile, but elevated levels of its M2 metabolite require further
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- * The study focused on CCL18, a chemokine linked to allergic diseases, revealing that it effectively stimulates NK cell migration and cytotoxicity in nonallergic individuals but not in those with allergies.
- * NK cells from allergic patients did not respond to CCL18, indicating a potential defect in their immune functions, while the inability to respond was not due to a problem with CCL18 binding.
The amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD). Preventing deregulated APP processing by inhibiting amyloidogenic processing of carboxy-terminal fragments (APP-CTFs), and reducing the toxic effect of amyloid beta (Aβ) peptides remain an effective therapeutic strategy. We report the design of piperazine-containing compounds derived from chloroquine structure and evaluation of their effects on APP metabolism and ability to modulate the processing of APP-CTF and the production of Aβ peptide.
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- Eosinophils are immune cells that play a key role in inflammation and require careful regulation to prevent tissue damage; their activation and apoptosis (programmed cell death) are essential for a proper immune response.* -
- This study investigates how Natural Killer (NK) cells affect eosinophils, finding that NK cells can activate eosinophils and trigger their degranulation and apoptosis through direct contact.* -
- The activation involves specific cell signaling pathways (MAPK and PI3K), increased reactive oxygen species, and suggests that mitochondrial function contributes to the apoptosis of eosinophils induced by NK cells.*
Background: The development of mucosal vaccines is crucial to efficiently control infectious agents for which mucosae are the primary site of entry. Major drawbacks of these protective strategies are the lack of effective mucosal adjuvant. Synthetic oligodeoxynucleotides that contain several unmethylated cytosine-guanine dinucleotide (CpG-ODN) motifs are now recognized as promising adjuvants displaying mucosal adjuvant activity through direct activation of TLR9-expressing cells.
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- Neonates have underdeveloped immune systems, making them susceptible to infections like Cryptosporidium parvum, prompting researchers to explore the use of oligodeoxynucleotides (ODNs) to enhance their immune response.
- In experiments with neonatal mice, treatment with CpG ODN 1668 (orally and intraperitoneally) significantly reduced parasite load by 80%-95% and stimulated the production of key cytokines in the intestine via a TLR9-dependent pathway.
- The study identified two effective mechanisms for reducing C. parvum infection: the well-established CpG/TLR9 interaction and a novel TLR9-independent method from non-CpG ODNs, demonstrating potential new strategies for
Article Synopsis
- Cryptosporidium parvum infection triggers the recruitment of various inflammatory cells, particularly T lymphocytes that produce interferon gamma, crucial for fighting the infection.
- Research indicates that beta7 integrin is not necessary for controlling the infection in mice overall.
- However, mice lacking beta7 integrin, specifically neonatal ones, show increased vulnerability during the initial stages of the infection.
The control of Listeria monocytogenes infection depends on the rapid activation of the innate immune system, likely through Toll-like receptors (TLR), since mice deficient for the common adapter protein of TLR signaling, myeloid differentiation factor 88 (MyD88), succumb to Listeria infection. In order to test whether TLR2 is involved in the control of infections, we compared the host response in TLR2-deficient mice with that in wild-type mice. Here we show that TLR2-deficient mice are more susceptible to systemic infection by Listeria than are wild-type mice, with a reduced survival rate, increased bacterial burden in the liver, and abundant and larger hepatic microabscesses containing increased numbers of neutrophils.
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