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1.
J Immunol ; 205(8): 2146-2155, 2020 10 15.
Article in English | MEDLINE | ID: mdl-32887748

ABSTRACT

Despite the fact that the majority of people in tuberculosis (TB)-endemic areas are vaccinated with the Bacillus Calmette-Guérin (BCG) vaccine, TB remains the leading infectious cause of death. Data from both animal models and humans show that BCG and subunit vaccines induce T cells of different phenotypes, and little is known about how BCG priming influences subsequent booster vaccines. To test this, we designed a novel Mycobacterium tuberculosis-specific (or "non-BCG") subunit vaccine with protective efficacy in both mice and guinea pigs and compared it to a known BCG boosting vaccine. In naive mice, this M. tuberculosis-specific vaccine induced similar protection compared with the BCG boosting vaccine. However, in BCG-primed animals, only the M. tuberculosis-specific vaccine added significantly to the BCG-induced protection. This correlated with the priming of T cells with a lower degree of differentiation and improved lung-homing capacity. These results have implications for TB vaccine design.


Subject(s)
Antigens, Bacterial/immunology , Cell Differentiation/immunology , Mycobacterium bovis/immunology , Mycobacterium tuberculosis/immunology , T-Lymphocytes , Tuberculosis , Animals , Female , Guinea Pigs , Mice , T-Lymphocytes/immunology , T-Lymphocytes/pathology , Tuberculosis/immunology , Tuberculosis/pathology , Tuberculosis/prevention & control , Vaccination
2.
Eur J Pharmacol ; 881: 173205, 2020 Aug 15.
Article in English | MEDLINE | ID: mdl-32442540

ABSTRACT

Vascular tissue consists of endothelial cells, vasoactive smooth muscle cells and perivascular nerves. The perivascular sensory neuropeptide CGRP has demonstrated potent vasodilatory effects in any arterial vasculature examined so far, and a local protective CGRP-circuit of sensory nerve terminal CGRP release and smooth muscle cell CGRP action is evident. The significant vasodilatory effect has shadowed multiple other effects of CGRP in the vascular tissue and we therefore thoroughly review vascular actions of CGRP on endothelial cells, vascular smooth muscle cells and perivascular nerve terminals. The actions beyond vasodilation includes neuronal re-uptake and neuromodulation, angiogenic, proliferative and antiproliferative, pro- and anti-inflammatory actions which vary depending on the target cell and anatomical location. In addition to the classical perivascular nerve-smooth muscle CGRP circuit, we review existing evidence for a shadowed endothelial autocrine pathway for CGRP. Finally, we discuss the impact of local and systemic actions of CGRP in vascular regulation and protection from hypertensive and ischemic heart conditions with special focus on therapeutic CGRP agonists and antagonists.


Subject(s)
Arteries/metabolism , Calcitonin Gene-Related Peptide/metabolism , Cardiovascular Diseases/metabolism , Receptors, Calcitonin Gene-Related Peptide/metabolism , Vasodilation , Animals , Arteries/drug effects , Arteries/innervation , Calcitonin Gene-Related Peptide/therapeutic use , Cardiovascular Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/physiopathology , Hormone Antagonists/therapeutic use , Humans , Receptors, Calcitonin Gene-Related Peptide/drug effects , Signal Transduction , Vasodilation/drug effects
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