Despite low levels of infection, human mast cells produce multiple chemokines in response to RSV through mechanisms that include responses to type I interferons. Such mast cell responses might enhance effector cell recruitment during RSV-induced disease.
Herpes simplex virus (HSV) types 1 and 2 cause several important syndromes, including congenital and perinatal infections that can cause devastating consequences in newborns (i.e., neonatal HSV). Most neonatal HSV infections are acquired intrapartum in the infected maternal birth canal. Since genital HSV infections are common, neonatal HSV is an important complication in infected women, even if maternal symptoms are absent. As a result of the developmental status of the fetal and newborn immune system, neonatal HSV infection is associated with life-threatening disease. This chapter reviews the clinical presentations of neonatal HSV infection, as well as advances in diagnosis and therapy. Skin vesicles and fever are often absent, which contributes to a delay in initiating effective therapy. Early recognition is key. Despite significant advances in diagnostic testing and antiviral treatment for neonatal HSV, morbidity and mortality remain high and no vaccine is currently available for clinical use.
BackgroundMast cells are resident immune effector cells, often studied in the context of allergic disease. Found in substantial numbers at sites of potential infection they are increased at sites of angiogenesis and can be pivotal for the sensing and clearance of a variety of pathogens. Interferons (IFNs) are cytokines that are critical for host defence against intracellular pathogens. Increased levels of IFNs are observed during viral infection and in autoimmune diseases. IFNs are also widely used therapeutically and have been examined in the therapy of severe asthma.ObjectiveTo define the selective human mast cell cytokine and chemokine response following activation with type I or type II IFN's.MethodsThe ability of both IFNα2 and IFNγ to induce cytokine production by human cord blood‐derived mast cells was examined in vitro. Cytokine and chemokine production at 6 and 24 h was assessed by multiplex protein analysis. Degranulation was assessed by β‐hexosaminidase release. Mast cells were also treated with reovirus or respiratory syncytial virus and their production of CXCL10, IL‐1 receptor antagonist (IL‐1Ra), and vascular endothelial growth factor (VEGF) examined after 24 h.ResultsIn addition to increased expression of classical IFN response genes, such as CXCL10, small but significant increases in CCL5 and IL‐17 production were observed following IFN activation. Notably, human mast cells produced both VEGF and IL‐1Ra in a dose dependent manner. These responses occurred in the absence of mast cell degranulation by a mechanism consistent with classical IFN signaling. Both reovirus and respiratory syncytial virus infection of mast cells, were also associated with IFN‐dependent IL‐1Ra expression.Conclusion and Clinical RelevanceOur findings demonstrate that IFNs have profound impact on cytokine and chemokine expression by human mast cells, alone or in the context of viral infection. Mast cell VEGF and IL‐1Ra responses to IFNs could impact the regulation of local inflammatory responses and subsequent tissue remodeling.
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