Association of pneumonia with concentrations of virulent Rhodococcus equi in fecal swabs of foals before and after intrabronchial infection with virulent R. equi

Abstract

Background: Intragastric administration of virulent Rhodococcus equi protects foals against subsequent experimental intrabronchial (IB) infection, but it is unknown whether R. equi naturally ingested by foals contributes to their susceptibility to pneumonia.Hypothesis: Fecal concentration of virulent R. equi before IB infection with R. equi is positively associated with protection from pneumonia in foals.Animals: Twenty-one university-owned foals.Methods: Samples were collected from experimental studies. Five foals were gavaged with live, virulent R. equi (LVRE) at age 2 and 4 days; the remaining 16 foals were not gavaged with LVRE (controls). Fecal swabs were collected from foals at ages 28 days, immediately before IB infection. Foals were monitored for clinical signs of pneumonia, and fecal swabs were collected approximately 2 weeks after IB infection. Swabs were tested by quantitative PCR for concentration of virulent R. equi (ie, copy numbers of the virulence-associated protein A gene [vapA] per 100 ng fecal DNA).Results: Fecal concentrations of virulent R. equi (vapA) before IB infection were significantly (P < .05) lower in control foals (25 copies/100 ng DNA [95% CI, 5 to 118 copies/100 ng DNA) that developed pneumonia (n = 8) than in healthy control foals (n = 8; 280 copies/100 ng DNA; 95% CI, 30 to 2552 copies/100 ng DNA) or those gavaged with LVRE (707 copies/100 ng DNA, 95% CI, 54 to 9207 copies/100 ng DNA).Conclusions and Clinical Importance: Greater natural ingestion of LVRE might contribute to protection against pneumonia among foals.

Enteral immunization with live bacteria reprograms innate immune cells and protects neonatal foals from pneumonia

“…Therefore, we speculate that the gut-lung axis is involved in enhancing immune responses and protecting against pneumonia induced by enteral R. equi . Additionally, the natural resistance to R. equi pneumonia observed in some foals ( 16, 24, 67 ) could be due to ingestion of fecal R. equi present in the farm environment because coprophagia is common in foals ( 68 ). These ingested R. equi could stimulate maturation of the innate immune system.…”

“…Although these results are exciting, our study has limitations. First, we were not able to definitively determine whether the enhanced innate immune response observed in immunized foals was due to either memory features of hematopoietic progenitor cells (trained immunity) or continuous R. equi stimulation in the gut (constant priming of innate immune responses) because R. equi survives for weeks in the gut after enteral administration ( 68 ). Both hypotheses need to be considered because there are similarities between immunization with enteral R. equi and BCG vaccine, which is a well-recognized inducer of trained immunity ( 9, 41, 50, 51 ).…”

“…We infected foals with R. equi at age 28 days using our non-lethal model (Fig. 1A) ( 24, 46, 67, 68 ). Briefly, we sedated foals using intravenous (IV) injection of xylazine (0.2 mg/kg) and butorphanol tartrate (0.04 mg/kg).…”

Protective immune responses against Rhodococcus equi : an innate immunity-focused review

“…Newborn foals are resistant to high doses of virulentR. equi delivered into the stomach, [92][93][94][95]125 and R. equi infection of other organs is often found concurrently with pulmonary infection. 29 Limited information is available about susceptibility in other species as models of infection.…”