Ocular hypertension secondary to obesity: cortisol, the missing piece of the pathophysiological puzzle?

Dear Editor,Obesity has nowadays become a global public health challenge due to its rapidly growing prevalence and interconnection with a wide spectrum of comorbidities.

The immunology of sickness metabolism

Everyone knows that an infection can make you feel sick.Although we perceive infection-induced changes in metabolism as a pathology,they are a part of a carefully regulated process that depends on tissue-specific interactions between the immune system and organs involved in the regulation of systemic homeostasis.Immune-mediated changes in homeostatic parameters lead to altered production and uptake of nutrients in circulation,which modifies the metabolic rate of key organs.This is what we experience as being sick.The purpose of sickness metabolism is to generate a metabolic environment in which the body is optimally able to fight infection while denying vital nutrients for the replication of pathogens.Sickness metabolism depends on tissue-specific immune cells,which mediate responses tailored to the nature and magnitude of the threat.As an infection increases in severity,so do the number and type of immune cells involved and the level to which organs are affected,which dictates the degree to which we feel sick.Interestingly,many alterations associated with metabolic disease appear to overlap with immune-mediated changes observed following infection.Targeting processes involving tissue-specific interactions between activated immune cells and metabolic organs therefore holds great potential for treating both people with severe infection and those with metabolic disease.In this review,we will discuss how the immune system communicates in situ with organs involved in the regulation of homeostasis and how this communication is impacted by infection.

Angiogenesis and osteopontin expression in paraskeletal myeloma with plasmablastic morphology and aggressive clinical course:a report of two cases

Extramedullary disease(EMD)of multiple myeloma(MM)can present as paraskeletal(paraosseous)plasmocytoma(PP)that arise from skeletal focal lesions or extramedullary plasmacytomas(EMP)that derive from hematogenous spread.The pathogenetic mechanisms that distinguish classical MM,PP,and EMP are still insufficiently known,as are the therapies that would be effective in EMD.The aim of this study was to evaluate immunohistochemically the angiogenesis,determined as microvessel density(MVD)and osteopontin expression in PP,of two patients with MM of plasmablastic morphology and an aggressive course of disease.We found high levels of MVD and osteopontin expression in both cases of PP.The role of angiogenesis and osteopontin in EMD should be clarified in future investigations,especially since there are no satisfactory therapeutic protocols for this form of multiple myeloma,and both of these biological factors can be the potential targets of new therapies.

Cytomegalovirus immune evasion by perturbation ot endosomal trafficking

Cytomegaloviruses （CMVs）, members of the herpesvirus family, have evolved a variety of mechanisms to evade the immune response to survive in infected hosts and to establish latent infection, They effectively hide infected cells from the effector mechanisms of adaptive immunity by eliminating cellular proteins （major histocompatibility Class I and Class II molecules） from the cell surface that display viral antigens to CD8 and CD4 T lymphocytes, CMVs also successfully escape recognition and elimination of infected cells by natural killer （NK） cells, effector cells of innate immunity, either by mimicking NK cell inhibitory ligands or by downregulating NK cell-activating ligands, To accomplish these immunoevasion functions, CMVs encode several proteins that function in the biosynthetic pathway by inhibiting the assembly and trafficking of cellular proteins that participate in immune recognition and thereby, block their appearance at the cell surface, However, elimination of these proteins from the cell surface can also be achieved by perturbation of their endosomal route and subsequent relocation from the cell surface into intracellular compartments, Namely, the physiological route of every cellular protein, including immune recognition molecules, is characterized by specific features that determine its residence time at the cell surface, In this review, we summarize the current understanding of endocytic trafficking of immune recognition molecules and perturbations of the endosomal system during infection with CMVs and other members of the herpesvirus family that contribute to their immune evasion mechanisms,

MCMV-based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination

Global pandemics caused by influenza or coronaviruses cause severe disruptions to public health and lead to high morbidity and mortality.There remains a medical need for vaccines against these pathogens.CMV(cytomegalovirus)is aβ-herpesvirus that induces uniquely robust immune responses in which remarkably large populations of antigen-specific CD8+T cells are maintained for a lifetime.Hence,CMV has been proposed and investigated as a novel vaccine vector for expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens.We generated two recombinant murine CMV(MCMV)vaccine vectors expressing hemagglutinin(HA)of influenza A virus(MCMV^(HA))or the spike protein of severe acute respiratory syndrome coronavirus 2(MCMV^(S)).A single injection of MCMVs expressing either viral protein induced potent neutralizing antibody responses,which strengthened over time.Importantly,MCMV^(HA)-vaccinated mice were protected from illness following challenge with the influenza virus,and we excluded that this protection was due to the effects of memory T cells.Conclusively,we show here that MCMV vectors induce not only long-term cellular immunity but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.