an-vitro-model-to-study-immune-responses-human-peripheral-blood

An <em>In vitro</em> Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection

Human respiratory syncytial  virus (HRSV) infections present a broad spectrum of disease severity, ranging  from mild infections to life-threatening ...

Radboud university medical center

The prevalence and distribution of pMEA-like elements in the genus Amycolatopsis was studied. For this purpose, a set of 95 recently isolated Amycolatopsis strains and 16 Amycolatopsis type strains were examined for the presence of two unique pMEA-sequences (repAM and traJ), encoding proteins essential for replication and conjugative transfer. Homologues of repAM and traJ were found in 10 and 26 of 111 investigated strains, respectively, a result which shows that pMEA-like sequences, though not very abundant, can be found in several Amycolatopsis strains. Phylogenetic analysis of the deduced RepAM and TraJ protein sequences revealed clustering with the protein sequences of either pMEA300 or pMEA100. Furthermore, two geographically different populations of pMEA-like elements were distinguished, one originating in Europe and the other in Australia and Asia. Linkage between the distribution of repAM and traJ and the chromosomal identifier, the 16S rRNA gene, indicated that these elements coevolved with their hosts, suggesting that they evolved in an integrated form rather than by horizontal gene transfer of the free replicating form.

Prevalence and distribution of nucleotide sequences typical for pMEA-like accessory genetic elements in the genus Amycolatopsis.

Historically, most research on infectious diseases has focused on infections with single pathogens. However, infections with pathogens often occur in the context of pre-existing viral and bacterial infections. Clinically, this is of particular relevance for coinfections with Streptococcus pneumoniae and influenza virus, which together are an important cause of global morbidity and mortality. In recent years new evidence has emerged regarding the underlying mechanisms of influenza virus-induced susceptibility to secondary pneumococcal infections, in particular regarding the sustained suppression of innate recognition of S. pneumoniae. Conversely, it is also increasingly being recognized that there is not a unidirectional effect of the virus on S. pneumoniae, but that asymptomatic pneumococcal carriage may also affect subsequent influenza virus infection and the clinical outcome. Here, we will review both aspects of pneumococcal influenza virus infection, with a particular focus on the age-related differences in pneumococcal colonization rates and invasive pneumococcal disease.

Interactions between Streptococcus pneumoniae and influenza virus: a mutually beneficial relationship?

Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM.

Influenza-induced inflammation drives pneumococcal otitis media.

Otitis media (OM) affects ≥80% of children before the age of three. OM can arise following co-infection with influenza A virus (IAV) and the bacterium Streptococcus pneumoniae. We have previously shown that H3 IAV strains (such as Udorn/72) induced a higher rate of bacterial OM than H1 strains (such as PR8/34). This was associated with more efficient replication of H3 strains in the middle ear.

Marrit N. Habets

Laboratory of Pediatric Infectious Diseases,
Department of Pediatrics,
Laboratory of Pediatric Infectious Diseases, Department of Pediatrics

Radboud university medical center

An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection

Marrit N. Habets

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Laboratory of Pediatric Infectious Diseases,Department of Pediatrics,Laboratory of Pediatric Infectious Diseases, Department of Pediatrics

Radboud university medical center

An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection

Laboratory of Pediatric Infectious Diseases,
Department of Pediatrics,
Laboratory of Pediatric Infectious Diseases, Department of Pediatrics