C-Type Lectin Receptor Mediated Modulation of T2 Immune Responses to Allergens.

PURPOSE OF REVIEW: Allergic diseases represent a major health problem of increasing prevalence worldwide. In allergy, dendritic cells (DCs) contribute to both the pathophysiology and the induction of healthy immune responses to the allergens. Different studies have reported that some common allergens contain glycans in their structure. C-type lectin receptors (CLRs) expressed by DCs recognize carbohydrate structures and are crucial in allergen uptake, presentation, and polarization of T cell responses. This review summarizes the recent literature regarding the role of CLRs in the regulation of type 2 immune responses to allergens. RECENT FINDINGS: In this review, we highlight the capacity of CLRs to recognize carbohydrates in common allergens triggering different signaling pathways involved in the polarization of CD4+ T cells towards specific Th2 responses. Under certain conditions, specific CLRs could also promote tolerogenic responses to allergens, which might well be exploited to develop novel therapeutic approaches of allergen-specific immunotherapy (AIT), the single treatment with potential disease-modifying capacity for allergic disease. At this regard, polymerized allergens conjugated to non-oxidized mannan (allergoid-mannan conjugated) are next-generation vaccines targeting DCs via CLRs that promote regulatory T cells, thus favoring allergen tolerance both in preclinical models and clinical trials. A better understanding of the role of CLRs in the development of allergy and in the induction of allergen tolerance might well pave the way for the design of novel strategies for allergic diseases.

Isolation and Culturing of Primary Mouse and Human Macrophages.

Macrophages are mature immune cells involved in the defense of the organism. Since their discovery, the main function attributed to macrophages has been phagocytosis. However, in recent years, several new functions such as angiogenesis, tissue remodeling, clearance of apoptotic cells, pro- and anti-inflammatory properties and tumor growth have been attributed to macrophages. To perform such varied functions, macrophages acquire specific phenotypes in response to external signals. The possibility of replicating these phenotypes in vitro represents a cutting-edge tool to understand potential macrophage functions in vivo. This chapter outlines protocols used to isolate and culture murine bone marrow-derived and human monocyte-derived macrophages. Furthermore, macrophage polarization processes into different phenotypes, with special relevance to atherosclerosis, are indicated.

Sustained Focal Vascular Inflammation Accelerates Atherosclerosis in Remote Arteries.

OBJECTIVE: Evidence from preclinical and clinical studies has demonstrated that myocardial infarction promotes atherosclerosis progression. The impact of focal vascular inflammation on the progression and phenotype of remote atherosclerosis remains unknown. Approach and Results: We used a novel ApoE-/- knockout mouse model of sustained arterial inflammation, initiated by mechanical injury in the abdominal aorta. Using serial in vivo molecular MRI and ex vivo histology and flow cytometry, we demonstrate that focal arterial inflammation triggered by aortic injury, accelerates atherosclerosis in the remote brachiocephalic artery. The brachiocephalic artery atheroma had distinct histological features including increased plaque size, plaque permeability, necrotic core to collagen ratio, infiltration of more inflammatory monocyte subsets, and reduced collagen content. We also found that arterial inflammation following focal vascular injury evoked a prolonged systemic inflammatory response manifested as a persistent increase in serum IL-6 (interleukin 6). Finally, we demonstrate that 2 therapeutic interventions-pravastatin and minocycline-had distinct anti-inflammatory effects at the plaque and systemic level. CONCLUSIONS: We show for the first time that focal arterial inflammation in response to vascular injury enhances systemic vascular inflammation, accelerates remote atheroma progression and induces plaques more inflamed, lipid-rich, and collagen-poor in the absence of ischemic myocardial injury. This inflammatory cascade is modulated by pravastatin and minocycline treatments, which have anti-inflammatory effects at both plaque and systemic levels that mitigate atheroma progression.

Molecular Imaging in Ischemic Heart Disease.

PURPOSE OF REVIEW: The purpose of this paper is to review current and new modalities to image key biological processes in ischemic heart disease and after myocardial infarction non-invasively. RECENT FINDINGS: New imaging targets have been developed to detect and quantify myocardial damage after ischemia. Although positron emission tomography (PET) has been leading the development of new probes in the past, continuous improvements of magnetic resonance imaging (MRI) together with the development of new novel MRI contrast agents opens new research avenues including the combination of both PET and MRI to obtain anatomic, functional, and molecular information simultaneously, which is not possible from a single imaging session. SUMMARY: This review summarizes the state of art of non-invasive molecular imaging of the myocardium during ischemia and after myocardial infarction using PET and MRI. We also describe the different contrast agents that have been developed to image the different phases of cardiac healing and the biological processes associated with each of those phases. Importantly, here we focus on imaging of inflammation as it is the key biological process that orchestrates clearance of dead cells, tissue remodeling, cardiac repair, and future outcome. We also focus on clinical translation of some of the novel contrast agents that have been tested in patients and discuss the need for larger, multi-center patient studies to fully validate the applicability of new imaging probes.

Molecular imaging of cardiac remodelling after myocardial infarction.

Myocardial infarction and subsequent heart failure is a major health burden associated with significant mortality and morbidity in western societies. The ability of cardiac tissue to recover after myocardial infarction is affected by numerous complex cellular and molecular pathways. Unbalance or failure of these pathways can lead to adverse remodelling of the heart and poor prognosis. Current clinical cardiac imaging modalities assess anatomy, perfusion, function, and viability of the myocardium, yet do not offer any insight into the specific molecular pathways involved in the repair process. Novel imaging techniques allow visualisation of these molecular processes and may have significant diagnostic and prognostic values, which could aid clinical management. Single photon-emission tomography, positron-emission tomography, and magnetic resonance imaging are used to visualise various aspects of these molecular processes. Imaging probes are usually attached to radioisotopes or paramagnetic nanoparticles to specifically target biological processes such as: apoptosis, necrosis, inflammation, angiogenesis, and scar formation. Although the results from preclinical studies are promising, translating this work to a clinical environment in a valuable and cost-effective way is extremely challenging. Extensive evaluation evidence of diagnostic and prognostic values in multi-centre clinical trials is still required.