Introduction: Macrophage-inducible C-type lectin (Mincle) has emerged as a potential contributor to neuropathic pain induction and neuroinflammatory responses within the spinal cord. Moreover, evidence suggests a close association between toll-like receptor (TLR) and Mincle expression in myeloid cells. This study evaluated the effectiveness of Mincle antibodies in neuropathic pain and identified the epitope of these antibodies. In addition, the mode of interaction between Mincle and TLR inhibition was explored using isobolographic analysis.
Methods: Three different Mincle antibodies and a specific TLR4 inhibitor (TAK-242) were intrathecally administered, and mechanical allodynia was evaluated using the von Frey test in a rat model of spinal nerve ligation (SNL). Isobolographic analysis was conducted on the effect of combination of TAK-242 and Mincle Ab. Microarray analysis examined the specific region of Mincle targeted by the antibodies.
Results: All Mincle antibodies and TAK-242 significantly alleviated mechanical allodynia in a dose-dependent manner. However, the maximal possible effects (MPE) produced by the antibodies ranged widely from 37.1 % to 91.8 %, comparable to that of TAK-242 (88.7 %). The combination of TAK-242 and the antibody with the highest MPE resulted in an additive interaction for their anti-allodynic effects. Epitope mapping revealed that each antibody targeted the extracellular domain, with epitope lengths ranging from 5 to 15 amino acids.
Conclusions: The current study demonstrates the anti-allodynic effect of Mincle antibodies and additive interaction with TLR4 inhibition in spinal nerve ligation model, suggesting the potential of blocking of Mincle signaling with its antibodies as a novel treatment strategy for neuropathic pain.
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http://dx.doi.org/10.1016/j.heliyon.2024.e40694 | DOI Listing |
Heliyon
December 2024
Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Gwangju, South Korea.
Introduction: Macrophage-inducible C-type lectin (Mincle) has emerged as a potential contributor to neuropathic pain induction and neuroinflammatory responses within the spinal cord. Moreover, evidence suggests a close association between toll-like receptor (TLR) and Mincle expression in myeloid cells. This study evaluated the effectiveness of Mincle antibodies in neuropathic pain and identified the epitope of these antibodies.
View Article and Find Full Text PDFInfect Immun
December 2024
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, the Thoracic Diseases Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
pneumonia (PJP) remains a significant cause of morbidity and mortality during AIDS. In AIDS, the absence of CD4 immunity results in exuberant and often fatal PJP. In addition, organism clearance requires a balanced macrophage response since excessive inflammation promotes lung injury and respiratory failure.
View Article and Find Full Text PDFActa Biomater
December 2024
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China. Electronic address:
Effective vaccination is crucial for intervening in the COVID-19 pandemic. However, with the continuous mutation of the SARS-CoV-2, existing vaccines including subunit vaccines cannot effectively prevent virus infections. Hence, there is an urgent need to enhance the immunogenicity of existing vaccines to induce a more potent and durable immune response.
View Article and Find Full Text PDFNat Commun
October 2024
Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen, Denmark.
Development of new vaccines tailored for difficult-to-target diseases is hampered by a lack of diverse adjuvants for human use, and none of the currently available adjuvants induce Th17 cells. Here, we develop a liposomal adjuvant, CAF®10b, that incorporates Mincle and Toll-like receptor 9 agonists. In parallel mouse and non-human primate studies comparing to CAF® adjuvants already in clinical trials, we report species-specific effects of adjuvant composition on the quality and magnitude of the responses.
View Article and Find Full Text PDFNPJ Vaccines
June 2024
Center for Translational Medicine, University of Montana, 32 Campus Drive, Missoula, MT, 59812, USA.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the top infectious killers in the world. The only licensed vaccine against TB, Bacille Calmette-Guérin (BCG), provides variable protection against pulmonary TB, especially in adults. Hence, novel TB vaccine approaches are urgently needed.
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