The nucleotide-binding domain (NBD) and leucine-rich repeat receptors, such as NOD-like receptors (NLRs), have pivotal functions in the innate immune response to various viral infections participating during the recognition of pathogens and activation of signaling pathways. One NLR, NOD2, is a dynamic protein that is activated in the presence of viral genomes and metabolites. However, its participation in combating a dengue virus (DENV) infection remains unclear. The aim of this study was to determine the role of NOD2 in macrophage-like THP-1 cells during an in vitro infection with DENV type 2 (DENV2). The interactions of NOD2 with RIP2 and MAVS was examined in DENV2-infected and agonist-stimulated cells. The effects of downregulating NOD2 expression or signaling on virus loads was also evaluated. The cellular mRNA expression and protein levels of NOD2 on cells under the stimuli were quantified with RT-PCR, Western blot and indirect immunofluorescence. Both the mRNA and protein expression of NOD2 was enhanced in response to DENV-2 infection. Interactions of NOD2 with RIP2 and MAVS, analyzed with confocal microscopy and co-immunoprecipitation assays, were time-dependent and increased in the post-infection period, between 6 and 24 h. After silencing NOD2 expression, DENV2-infected cells displayed greater viral loads and decreased expression of IL-8 and IFN-α (measured in supernatants obtained from the cells), compared to the uninfected (mock control) cells or those transfected with irrelevant-siRNA. Thus, in response to a DENV2 infection, NOD2 was activated in THP-1 human macrophage-like cells, the production of IL-8 and IFN-α was enhanced, and viral replication was limited.
Introduction: Respiratory Syncytial Virus (RSV) is the main causative agent of respiratory tract infections at pediatric ages in Mexico and around the world. In our study we determine and correlating clinics characteristics to the levels of specific IgA against RSV in respiratory samples for infected children and the absence or presence of exclusive breastfeeding. Material and methods: This is a clinical, ambispective and comparative study. There were included all patients pediatrics hospitalized and the samples of nasopharyngeal exudate were obtained, there was performed an ELISA on them with a Human Respiratory Syncytial Virus to determine the levels of specific IgA against RSV. Results: The total of patients included was 197. Finding that only 4.1% of infants received a complete vaccination schedule. Up to 22.8% were coinfected with a virus upon admission. There was found a significant difference in the rate of oxygenation during the admission presented by lactated vs non-lactated patients (p 0.002), as well as the presence of crackles p = 0.029 (95% CI 0.502-0.095) and wheezing p = 0.043 (95% CI 0.522-0.980), and a difference between the levels of specific IgA and the personal history of repeated respiratory tract infections (p = 0.018). Differences in symptoms such as dry cough, thoracoabdominal dissociation (p = 0.043, p = 0.044 respectively), were found as well. Conclusions: The results obtained from this research lead to stablish that low levels of specific IgA against RSV in the airways, are statistically and clinically related to greater severity of RSV infection.