Abstract: Rhodococcal pneumonia is an important disease of young horses that is not seen in immunocompetent adults. Since all foals are normally exposed to Rhodococcus equi in their environment, we hypothesized that most develop protective immune responses. Furthermore, these antigen-specific responses were hypothesized to operate throughout adult life to prevent rhodococcal pneumonia. A better understanding of the mechanisms of immune clearance in adult horses would help define the requirements for an effective vaccine in foals. Adult horses were challenged with virulent R. equi by intrabronchial inoculation into the right lung, and pulmonary immune responses were followed for 2 weeks by bronchoalveolar lavage. Local responses in the inoculated right lung were compared to the uninfected left lung and peripheral blood. Challenged horses rapidly cleared R. equi infection without significant clinical signs. Clearance of bacteria was associated with increased mononuclear cells in bronchoalveolar lavage fluid (primarily lymphocytes) and inversion of the normal macrophage:lymphocyte ratio. There was no significant increase in neutrophils at 7 days post-challenge. Flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that clearance correlated with significant increases in pulmonary T-lymphocytes, both CD4+ and CD8+. Prior to challenge, most adult horses demonstrated low proliferative responses when pulmonary lymphocytes were stimulated with soluble R. equi ex vivo. However, clearance was associated with marked increases in lymphoproliferative responses to soluble R. equi antigen and recombinant VapA, a virulence associated protein of R. equi and candidate immunogen. These results are compatible with previous work in mice which showed that both CD4+ and CD8+ T-cells play a role in immune clearance of R. equi. Recognition of VapA in association with clearance lends further support to its testing as an immunogen. Importantly, the cellular responses to R. equi challenge were relatively compartmentalized. Responses were more marked and the sensitivity to antigen dose was increased at the site of challenge. The blood, including peripheral blood mononuclear cells, was an insensitive indicator of local pulmonary responses.
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The research investigates how adult horses resist Rhodococcus equi, the bacterium causing rhodococcal pneumonia, focusing on the immune responses in their lungs. It demonstrates that these horses can rapidly clear the infection, which provides evidence to support the creation of an effective vaccine for foals.
Research Hypothesis
The study was based on the belief that most foals develop protective immune responses to Rhodococcus equi, a bacterium they are routinely exposed to in their environments. These reactive immune responses were hypothesized to carry on throughout the adult life of these horses, preventing the development of rhodococcal pneumonia.
Understanding the principles of immune clearance in adult horses could give a significant foundation for creating an efficient vaccine for foals, who are most vulnerable to the disease.
Study Methodology
The researchers infected adult horses with virulent Rhodococcus equi by inoculating it directly into the right lung.
The pulmonary immune responses were monitored for two weeks by using bronchoalveolar lavage, a method for examining the airways.
The responses in the inoculated right lung were then compared to those in the uninfected left lung and blood circulating in the peripheral area.
Results and Observations
the infected horses cleared the R. equi infection quickly and without displaying significant clinical indicators of illness.
the bacteria’s clearance was linked with an increase in mononuclear cells (mainly lymphocytes) in the fluid retrieved from bronchoalveolar lavage and the normal ratio of macrophage to lymphocyte was reversed.
no significant rise in neutrophils was noted seven days post-infection.
analysis demonstrated that the bacteria’s clearance was linked with a significant increase in the pulmonary T-lymphocytes, both CD4+ and CD8+ types.
the clearance also correlated with marked increases in lymphoproliferative responses to the R. equi antigen and recombinant VapA antigen, a protein associated with the virulence of R. equi and a potential candidate for an immunogen.
Conclusions and Future Work
the observed immune response supports the previous tests conducted on mice, which deduced that both CD4+ and CD8+ T-cells are critical in clearing the R. equi infection.
the successful recognition of VapA antigen as part of the clearance process further underscores its potential as an immunogen for future testing.
it was noticed that cellular responses to the R. equi challenge were relatively compartmentalized, with responses being more marked and sensitivity to antigen dose being increased at the site of the challenge.
the peripheral blood and associated mononuclear cells were found to be poor indicators of local pulmonary responses.
Cite This Article
APA
Hines MT, Paasch KM, Alperin DC, Palmer GH, Westhoff NC, Hines SA.
(2001).
Immunity to Rhodococcus equi: antigen-specific recall responses in the lungs of adult horses.
Vet Immunol Immunopathol, 79(1-2), 101-114.
https://doi.org/10.1016/s0165-2427(01)00258-6
Liu L, Cai P, Gu W, Duan X, Gao S, Ma X, Ma Y, Ma S, Li G, Wang X, Cai K, Wang Y, Cai T, Zhao H. Evaluation of vaccine candidates against Rhodococcus equi in BALB/c mice infection model: cellular and humoral immune responses. BMC Microbiol 2024 Jul 8;24(1):249.
Oliviero M, Iaccarino D, Esposito E, Paduano G, Di Nocera F, Borriello G, Paradiso R, Degli Uberti B, Dimatteo M, Amoroso MG, Lucifora G, Fusco G, De Carlo E. First description of Rhodococcus equi infection in common bottlenose dolphin (Tursiops truncatus). Vet Res Commun 2024 Jun;48(3):1949-1953.