Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infections in children and the elderly. The mechanism by which this virus triggers an inflammatory response still remains unknown. Here, we evaluated whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung inflammation upon hMPV infection. We found that hMPV infection promotes TSLP expression both in human airway epithelial cells and in the mouse lung. hMPV infection induced lung infiltration of OX40L + CD11b + DCs. Mice lacking the TSLP receptor deficient mice (tslpr −/− ) showed reduced lung inflammation and hMPV replication. These mice displayed a decreased number of neutrophils as well a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5, IL-13, and TNF-α in the airways upon hMPV infection. Furthermore, a higher frequency of CD4 + and CD8 + T cells was found in tslpr −/− mice compared to WT mice, which could contribute to controlling viral spread. Depletion of neutrophils in WT and tslpr −/− mice decreased inflammation and hMPV replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung inflammation and viral replication following hMPV challenge in mice. Altogether, these results suggest that activation of the TSLP pathway is pivotal in the development of pulmonary pathology and pulmonary hMPV replication.Keywords: Dendritic cells r hMPV r Inflammation r Neutrophils r OX40L r TSLP r Viral replication Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Alexis M. Kalergis e-mail: akalergis@bio.puc.cl * These authors contributed equally to this work.C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 1680-1695 Immunity to infection 1681 IntroductionHuman metapneumovirus (hMPV) is an enveloped virus that belongs to the Paramyxoviridae family, Pneumovirinae subfamily, and the Metapneumovirus genus. The hMPV genome consists of a 13.3-kb single-stranded, negative-sense RNA encoding eight messenger RNAs, which are transcribed directly from the viral genome and translated into nine different polypeptides [1,2]. hMPV was described for the first time in 2001 as a pathogen responsible for acute respiratory tract infections in children [3]. Today, hMPV is considered the second most relevant etiological agent of acute upper and lower respiratory tract infections in children, the elderly, and immunocompromised adults [4]. Furthermore, in young children, hMPV is the second most reported cause of bronchiolitis and pneumonia after human respiratory syncytial virus (hRSV), accounting for ß10% of pediatric hospitalizations related to acute respiratory tract infection [5][6][7]. In addition, hMPV is the cause of outbreaks of acute respiratory tract infections with more than 10% mortality in elderly patients [8,9]. Currently, neither safe-effective vaccines nor specific antiviral therapies are available for hMPV, although promising candidate vaccines have recently be...

Among subjects with mild COPD, those with daily-life dyspnea have worse exercise outcomes; distinct lung and thigh muscle morphologic features; and different pulmonary physiologic characteristics at rest and exercise. ΔIC was the main contributor to dyspnea intensity and ΔIC and thigh muscle wasting were determinants of exercise capacity.

Based on the results of various immunization strategies and therapeutic approaches, it is likely that the most effective strategy against hRSV will be a prophylactic tool aimed at developing a strong antiviral T-cell response capable of both, promoting the generation of hRSV-specific high affinity antibodies and leading the protective immunity required to prevent the disease caused by this virus. Alternatively, if prophylactic strategies fail, antiviral drugs and novel passive immunity strategies could significantly contribute to reducing hospitalization rates in susceptible individuals.