Permissiveness of Guinea Pig Alveolar Macrophage Subpopulations to Acute Respiratory Syncytial Virus Infection In Vitro: Discussion

In: Respiratory

30 Jul 2014

Permissiveness of Guinea Pig Alveolar Macrophage Subpopulations to Acute Respiratory Syncytial Virus Infection In Vitro: DiscussionFurther analysis by immunogold labeling provided qualitative information about patterns of virus-cell interactions that may be pertinent to the ability of the different AM subpopulations to support or restrict viral replication. In particular, immunolabeling within the phagolysosomes of hypodense AMs correlates with the granular staining pattern observed under light microscopy and is consistent with this subpopulation of cells preferentially inactivating the virus. In contrast, the distribution of gold particles free within the cytoplasm and in association with viral nucleocapsids may be related to the greater tendency of intermediate-density and high-density cells to support viral replication.
Restriction of in vitro RSV replication has been reported previously in unfractionated human AMs obtained from adults. The mechanisms of this restricted viral replication in adults remain unclear although they could involve production of cytokines such as tumor necrosis factor-a by infected cells. Canadian health&care mall Reading here The results of this study suggest diat restriction of RSV replication in humans is likely modulated by the subpopulation of hypodense AMs, where compartmental-ization of virus within phagolysosomes may be involved in addition to virus-induced production of cytokines.
We speculate that these differences in RSV-cell interactions between AM subpopulations, reported in this study, may be an important factor that could determine the susceptibility of an individual to develop severe or limited RSV lower respiratory tract infections. Since most AMs in the lungs of normal adults are hypodense, effective restriction of viral replication by these cells might confer protection that limits of the severity of RSV infection. By contrast, the relative proportions of high-density and hypodense AMs in the alveolar space of children are unknown, and if children have a predominant population of high-density AMs, then this milieu might support increased viral replication and further contribute to more severe lower respiratory tract infections.
In summary, this study has demonstrated that the permissiveness of AM subpopulations to acute RSV infection in vitro is inversely related to their degree of maturation achieved in vivo, where comparatively immature, high-density AMs support viral replication and mature, hypodense AMs may restrict viral replication. An improved understanding of the mechanisms responsible for these different virus-cell interactions may help to develop innovative approaches for the prevention and treatment of severe RSV lower respiratory tract infections.


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