BackgroundHuman parainfluenza viruses (HPIVs) are important causes of upper respiratory tract illness (URTI) and lower respiratory tract illness (LRTI). To analyse epidemiologic and clinical characteristics of the four types of human parainfluenza viruses (HPIVs), patients with acute respiratory tract illness (ARTI) were studied in Guangzhou, southern China.MethodsThroat swabs (n=4755) were collected and tested from children and adults with ARTI over a 26-month period, and 4447 of 4755 (93.5%) patients’ clinical presentations were recorded for further analysis.ResultsOf 4755 patients tested, 178 (3.7%) were positive for HPIV. Ninety-nine (2.1%) samples were positive for HPIV-3, 58 (1.2%) for HPIV-1, 19 (0.4%) for HPIV-2 and 8 (0.2%) for HPIV-4. 160/178 (88.9%) HPIV-positive samples were from paediatric patients younger than 5 years old, but no infant under one month of age was HPIV positive. Seasonal peaks of HPIV-3 and HPIV-1 occurred as autumn turned to winter and summer turned to autumn. HPIV-2 and HPIV-4 were detected less frequently, and their frequency of isolation increased when the frequency of HPIV-3 and HPIV-1 declined. HPIV infection led to a wide spectrum of symptoms, and more “hoarseness” (p=0.015), “abnormal pulmonary breathing sound” (p<0.001), “dyspnoea” (p<0.001), “pneumonia” (p=0.01), and “diarrhoea” (p<0.001) presented in HPIV-positive patients than HPIV-negative patients. 10/10 (100%) HPIV-positive adult patients (≥14 years old) presented with systemic influenza-like symptoms, while 90/164 (54.9%) HPIV-positive paediatric patients (<14 years old) presented with these symptoms (p=0.005). The only significant difference in clinical presentation between HPIV types was “Expectoration” (p<0.001). Co-infections were common, with 33.3%–63.2% of samples positive for the four HPIV types also testing positive for other respiratory pathogens. However, no significant differences were seen in clinical presentation between patients solely infected with HPIV and patients co-infected with HPIV and other respiratory pathogens.ConclusionsHPIV infection led to a wide spectrum of symptoms, and similar clinical manifestations were found in the patients with four different types of HPIVs. The study suggested pathogenic activity of HPIV in gastrointestinal illness. The clinical presentation of HPIV infection may differ by patient age.

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Locus ceruleus (LC) is the main subcortical site of norepinephrine synthesis. In Alzheimer's disease (AD) patients and rodent models, degeneration of LC neurons and reduced levels of norepinephrine in LC projection areas are significantly correlated with the increase in amyloid plaques, neurofibrillary tangles, and severity of dementia. Activated microglia play a pivotal role in the progression of AD by either clearing amyloid ␤ peptide (A␤) deposits through uptake of A␤ or releasing cytotoxic substances and proinflammatory cytokines. Here, we investigated the effect of norepinephrine on A␤ uptake and clearance by murine microglia and explored the underlying mechanisms. We found that murine microglia cell line N9 and primary microglia expressed ␤ 2 adrenergic receptor (AR) but not ␤ 1 and ␤ 3 AR. Norepinephrine and isoproterenol upregulated the expression of A␤ receptor mFPR2, a mouse homolog of human formyl peptide receptor FPR2, through activation of ␤ 2 AR in microglia. Norepinephrine also induced mFPR2 expression in mouse brain. Activation of ␤ 2 AR in microglia promoted A␤ 42 uptake through upregulation of mFPR2 and enhanced spontaneous cell migration but had no effect on cell migration in response to mFPR2 agonists. Furthermore, activation of ␤ 2 AR on microglia induced the expression of insulin-degrading enzyme and increased the degradation of A␤ 42 . Mechanistic studies showed that isoproterenol induced mFPR2 expression through ERK1/2-NF-B and p38-NF-B signaling pathways. These findings suggest that noradrenergic innervation from LC is needed to maintain adequate A␤ uptake and clearance by microglia, and norepinephrine is a link between neuron and microglia to orchestrate the host response to A␤ in AD.