Differential roles of CCL2 and CCR2 in host defense to coronavirus infection

The CC chemokine ligand 2 (CCL2, monocyte chemoattractant protein-1) is important in coordinating the immune response following microbial infection by regulating T cell polarization as well as leukocyte migration and accumulation within infected tissues. The present study examines the consequences of mouse hepatitis virus (MHV) infection in mice lacking CCL2 (CCL2(-/-)) in order to determine if signaling by this chemokine is relevant in host defense. Intracerebral infection of CCL2(-/-) mice with MHV did not result in increased morbidity or mortality as compared to either wild type or CCR2(-/-) mice and CCL2(-/-) mice cleared replicating virus from the brain. In contrast, CCR2(-/-) mice displayed an impaired ability to clear virus from the brain that was accompanied by a reduction in the numbers of antigen-specific T cells as compared to both CCL2(-/-) and wild-type mice. The paucity in T cell accumulation within the central nervous system (CNS) of MHV-infected CCR2(-/-) mice was not the result of either a deficiency in antigen-presenting cell (APC) accumulation within draining cervical lymph nodes (CLN) or the generation of virus-specific T cells within this compartment. A similar reduction in macrophage infiltration into the CNS was observed in both CCL2(-/-) and CCR2(-/-) mice when compared to wild-type mice, indicating that both CCL2 and CC chemokine receptor 2 (CCR2) contribute to macrophage migration and accumulation within the CNS following MHV infection. Together, these data demonstrate that CCR2, but not CCL2, is important in host defense following viral infection of the CNS, and CCR2 ligand(s), other than CCL2, participates in generating a protective response.     

X-linked liver glycogenosis type II (XLG II) is caused by mutations in PHKA2, the gene encoding the liver alpha subunit of phosphorylase kinase

X-linked liver glycogenosis type II (XLG II) is a recently described X- linked liver glycogen storage disease, mainly characterized by enlarged liver and growth retardation. These clinical symptoms are very similar to those of XLG I. In contrast to XLG I patients, however, XLG II patients do not show an in vitro enzymatic deficiency of phosphorylase kinase (PHK). Recently, mutations were identified in the gene encoding the liver alpha subunit of PHK (PHKA2) in XLG I patients. We have now studied the PHKA2 gene of four unrelated XLG II patients and identified four different mutations in the open reading frame, including a deletion of three nucleotides, an insertion of six nucleotides and two missense mutations. These results indicate that XLG II is due to mutations in PHKA2. In contrast to XLG I, XLG II is caused by mutations that lead to minor structural abnormalities in the primary structure of the liver alpha subunit of PHK. These mutations are found in a conserved RXX(X)T motif, resembling known phosphorylation sites that might be involved in the regulation of PHK. These findings might explain why the in vitro PHK enzymatic activity is not deficient in XLG II, whereas it is in XLG I.      

Eosinophils contribute to IL-4 production and shape the T-helper cytokine profile and inflammatory response in pulmonary cryptococcosis

Susceptibility to infection with Cryptococcus neoformans is tightly determined by production of IL-4. In this study, we investigated the time course of IL-4 production and its innate cellular source in mice infected intranasally with C. neoformans. We show that pulmonary IL-4 production starts surprisingly late after 6 weeks of infection. Interestingly, in the lungs of infected mice, pulmonary T helper (Th) cells and eosinophils produce significant amounts of IL-4. In eosinophil-deficient ΔdblGATA mice, IL-33 receptor-expressing Th2s are significantly reduced, albeit not absent, whereas protective Th1 and Th17 responses are enhanced. In addition, recruitment of pulmonary inflammatory cells during infection with C. neoformans is reduced in the absence of eosinophils. These data expand previous findings emphasizing an exclusively destructive effector function by eosinophilic granulocytes. Moreover, in ΔdblGATA mice, fungal control is slightly enhanced in the lung; however, dissemination of Cryptococcus is not prevented. Therefore, eosinophils play an immunoregulatory role that contributes to Th2-dependent susceptibility in allergic inflammation during bronchopulmonary mycosis.     

Effects of Expanded Cardiac Rehabilitation on Psychosocial Status in Coronary Artery Disease with Focus on Type D Characteristics

Type D personality has been shown to increase the risk for cardiovascular events in patients with coronary artery disease (CAD). We investigated the effects of expanded cardiac rehabilitation on type D score and psychosocial characteristics in 224 CAD patients randomised to either expanded cardiac rehabilitation (stress management, increased physical training, stay at a “Patient Hotel” after discharge and cooking sessions), or routine rehabilitation. Follow-up was 1 year. At baseline patients with a high type D score [patients in the upper quartile of type D score (Q4) i.e., type D patients] had a lower sense of coherence (p < 0.001), a lower quality of life (p < 0.001), more depressive symptoms (p < 0.001) and increased anxiety (p < 0.001) as compared to patients with a low type D score (Q1). During follow-up, type D patients (Q4) randomised to intervention had significant decrements in type D-score (p < 0.01), depression and anxiety (p < 0.05) and an increment in quality of life scores (p < 0.001). Quality of life was also improved in control type D patients (Q4; p < 0.01) but no significant changes were seen in type D score, depression or anxiety. Expanded cardiac rehabilitation reduces type D score, anxiety and depressive symptoms, and improves the quality of life in type D patients.     

Diagnostic performance of four SARS-CoV-2 antibody assays in patients with COVID-19 or with bacterial and non-SARS-CoV-2 viral respiratory infections

European Journal of Clinical Microbiology & Infectious Diseases - SARS-CoV-2 antibody assays are used for epidemiological studies and for the assessment of vaccine responses in highly...     

Correction to: Diagnostic performance of four SARS-CoV-2 antibody assays in patients with COVID-19 or with bacterial and non-SARS-CoV-2 viral respiratory infections

European Journal of Clinical Microbiology & Infectious Diseases -     

Clinical diagnosis of acute bacterial rhinosinusitis, typical of experts

Background  Clinical diagnosis of acute bacterial sinusitis (ABS) is a concern when a patient presents with nasal discharge of recent onset together with facial pain or pressure. Given this presentation, the doctor would benefit from having access to software that specifies, first, what diagnostic indicators experts typically use in that diagnosis and then, upon entry of those facts, what experts' typical probability of ABS is in such a case.
Methods  We specified a set of 23 hypothetical presentations of this type by patients 20–75 years of age, involving a comprehensive set of clinical-diagnostic indicators. Members of an international expert panel independently set the probability of ABS in each of these cases. A logistic function of the diagnostic indicators was fitted to the medians of the probabilities.
Results  The fitting led to an expression of the experts' median probability of ABS as a joint function of the duration of the patient's facial pain/pressure, and indicators of the location(s) of this; indicators of exacerbation of the pain/pressure on bending forward, nasal obstruction, maxillary and/or frontal tenderness, pus from middle meatus, purulent postnasal drip, and fever; and indicators of recent upper respiratory tract infection, nasal polyposis and status post sinus surgery. This probability function is accessible at http://www.evimed.ch/ABS .
Interpretation  That probability function, made readily accessible, provides for expertly probability setting in clinical diagnosis of ABS, relevant for decisions about further diagnostics or treatment without further tests.