Effects of age and macrophage lineage on intracellular survival and cytokine induction after infection with Rhodococcus equi.

This research studies how age and type of immune cell (macrophage lineage) influence the survival of a pathogen, Rhodococcus equi, and its ability to stimulate an immune response (cytokine induction). Rhodococcus equi causes serious lung infections and is dangerous for young horses (foals) and immunocompromised individuals.

Background and Aims

• The purpose of this study was to understand how the type of immune cell (macrophage lineage – monocyte-derived and bronchoalveolar) and the age of the host (horse) affects the survival and subsequent replication of Rhodococcus equi, a harmful pathogen.
• The researchers hypothesized that both the specific type of macrophage and the age of the host would significantly influence the intracellular survival of Rhodococcus equi and the level of immune response after infection.

Methods

• The study used monocyte-derived and bronchoalveolar macrophages taken from 10 adult horses and 10 foals of varying ages (1-3 days, 2 weeks, 1 month, 3 months, and 5 months).
• These macrophages were infected ex vivo (outside the body) with virulent Rhodococcus equi.
• The researchers then quantified the Rhodococcus equi within the cells and measured the mRNA expression of various cytokines – proteins that regulate immune response.

Results

• Rhodococcus equi replication was significantly higher in bronchoalveolar macrophages than in monocyte-derived macrophages, regardless of the age of the horse.
• Within any cell type, the replication of R. equi was significantly higher in 3-month-old foals compared to those aged 3-days, 2-weeks, 1-month, and to adult horses.
• The expression of certain cytokines was significantly higher in specific macrophages: IL-4 in monocyte-derived macrophages and IL-6, IL-18, and TNF-α in bronchoalveolar macrophages.
• There was greater induction of IL-1β, IL-10, IL-12 p40, and IL-8 mRNA in bronchoalveolar macrophages from 1-3-day old foals than in older foals or adult horses.

Conclusion and Implications

• Rhodococcus equi infection and subsequent intracellular survival was affected by both the age of the host and the lineage of macrophages, confirming the study hypothesis.
• The fact that Rhodococcus equi was found to preferentially survive within bronchoalveolar macrophages of young horses suggests a potential reason for the pathogen’s tendency to infect lungs and a reason behind the higher susceptibility of young horses to the infection.