Evaluation of equine immunoglobulin specific for Rhodococcus equi virulence-associated proteins A and C for use in protecting foals against Rhodococcus equi-induced pneumonia

Hooper-McGrevy, Kathleen; Giguère, S.; Wilkie, B.N.; Prescott, John F.

doi:10.2460/ajvr.2001.62.1307

Cited by 67 publications

(55 citation statements)

References 36 publications

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“…3) measure the ability of the organism to survive the innate immunity provided by macrophages. The observed attenuation of R. equi Ace-21 in these models was supported by infection studies with 3-week-old foals, in which the aceA mutant was found to be completely attenuated, since clinical and pathological findings were similar to those associated with infection of foals with a virulence plasmid-negative and therefore avirulent isolate (8,15).…”

Section: Discussionmentioning

confidence: 54%

Isocitrate Lyase Activity Is Required for Virulence of the Intracellular Pathogen Rhodococcus equi

Wall¹,

Duffy

Dupont

et al. 2005

Infect Immun

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Rhodococcus equi is an important pathogen of foals, causing severe pyogranulomatous pneumonia. Virulent R. equi strains grow within macrophages, a process which remains poorly characterized. A potential source of carbon for intramacrophage R. equi is membrane lipid-derived fatty acids, which following ␤ oxidation are assimilated via the glyoxylate bypass. To assess the importance of isocitrate lyase, the first enzyme of the glyoxylate bypass, in virulence of a foal isolate of R. equi, a mutant was constructed by a strategy of single homologous recombination using a suicide plasmid containing an internal fragment of the R. equi aceA gene encoding isocitrate lyase. Complementation of the resulting mutant with aceA showed that the mutant was specific for this gene. Assessment of virulence in a mouse macrophage cell line showed that the mutant was killed, in contrast to the parent strain. Studies in the liver of intravenously infected mice showed enhanced clearance of the mutant. When four 3-week-old foals were infected intrabronchially, the aceA mutant was completely attenuated, in contrast to the parent strain. In conclusion, the aceA gene was shown to be essential for virulence of R. equi, suggesting that membrane lipids may be an important source of carbon for phagocytosed R. equi.

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Section: Discussionmentioning

confidence: 54%

Isocitrate Lyase Activity Is Required for Virulence of the Intracellular Pathogen Rhodococcus equi

Wall¹,

Duffy

Dupont

et al. 2005

Infect Immun

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“…Although antibody provides partial protection against R. equi pneumonia (14), the role of the Ig isotype has not been described. Prescott et al determined that the antibody response of young foals to the APTX antigen with aluminium hydroxide adjuvant induced a more IgGb-and IgGT-biased subisotype response than did natural infection, which induced an IgGa-dominant response (30).…”

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confidence: 99%

Immunoglobulin G Subisotype Responses of Pneumonic and Healthy, Exposed Foals and Adult Horses toRhodococcus equiVirulence-Associated Proteins

Hooper-McGrevy

Wilkie

Prescott

2003

Clin Vaccine Immunol

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Rhodococcus equi causes severe pyogranulomatous pneumonia in foals and in immunocompromised humans. Replication of virulent isolates within macrophages correlates with the presence of a large plasmid which encodes a family of seven virulence-associated proteins (VapA and VapC to VapH), whose functions are unknown. Although cell-mediated immunity is thought to be crucial in eliminating R. equi infection, antibody partially protects foals. The antibody response to both VapA and VapC was similar in six adult horses and six naturally exposed but healthy foals, as well as in eight foals with R. equi pneumonia. The immunoglobulin G (IgG) subisotype response of pneumonic foals to Vap proteins was significantly IgGb biased and also had a trend toward higher IgGT association compared to the isotype association of antibody in adult horses and healthy exposed foals. This suggests that in horses, IgGb and IgGT are Th2 isotypes and IgGa is a Th1 isotype. Furthermore, it suggests that foals which develop R. equi pneumonia have a Th2-biased, ineffective immune response whereas foals which become immune develop a Th1-biased immune response. Pneumonic foals had significantly more antibody to VapD and VapE than did healthy exposed foals. This may indicate a difference in the expression of these two Vap proteins during persistent infection. Alternatively, in pneumonic foals the deviation of the immune response toward VapD and VapE may reflect a bias unfavorable to R. equi resistance. These data indicate possible age-related differences in the equine immune response affecting Th1-Th2 bias as well as antibody specificity bias, which together favor the susceptibility of foals to R. equi pneumonia.

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“…Evidence for a role of antibody in protection against R. equi is the protective effect of passively transferred anti-R. equi hyperimmune equine plasma which is used extensively on endemically affected farms to reduce morbidity and mortality. Hooper-McGrevy et al [36] showed that purified VapA-and VapC-antibody provided protection of foals against experimental pneumonic infection equivalent to that obtained with hyperimmune plasma. Interestingly, however, foals born to vaccinated mares are not protected against infection despite passive transfer of R. equi antibody.…”

Section: Immunitymentioning

confidence: 97%

Rhodococcus equi

2004

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-Rhodococcus equi is an important cause of subacute or chronic abscessating bronchopneumonia of foals up to 3-5 months of age. It shares the lipid-rich cell wall envelope characteristic of the mycolata, including Mycobacterium tuberculosis, as well as the ability of pathogenic members of this group to survive within macrophages. The possession of a large virulence plasmid in isolates recovered from pneumonic foals is crucial for virulence. The plasmid contains an 27 kb pathogenicity island (PI) that encodes seven related virulence-associated proteins (Vaps), including the immunodominant surface-expressed protein, VapA. Only PI genes are differentially expressed when the organism is grown in macrophages in vitro. Ten of the PI genes, including six Vap genes, have signal sequences, suggesting that they are exported from the cell to interact with the macrophage. Different PI genes are regulated by temperature, pH, iron, oxidative stress and probably also by magnesium, all environmental changes encountered after environmental R. equi are inhaled in dust and are ingested into macrophages in the lung. The basis of pathogenicity of R. equi is its ability to multiply in and eventually to destroy alveolar macrophages. Infectivity is largely or exclusively limited to cells of the monocyte-macrophage lineage. Current evidence suggests that infection of foals with virulent R. equi results in some foals in subversion of cellmediated immunity and development of an ineffective and sometimes lethal Th2-based immune response. Significant progress has been made recently in the development of R. equi-E. coli shuttle vectors, transformation and random and site specific mutagenesis procedures, all of which will be important in molecular dissection of the mechanisms by which R. equi subverts normal macrophage killing mechanisms and cell-mediated immunity.

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Evaluation of equine immunoglobulin specific for Rhodococcus equi virulence-associated proteins A and C for use in protecting foals against Rhodococcus equi-induced pneumonia

Cited by 67 publications

References 36 publications

Isocitrate Lyase Activity Is Required for Virulence of the Intracellular Pathogen Rhodococcus equi

Isocitrate Lyase Activity Is Required for Virulence of the Intracellular Pathogen Rhodococcus equi

Immunoglobulin G Subisotype Responses of Pneumonic and Healthy, Exposed Foals and Adult Horses toRhodococcus equiVirulence-Associated Proteins

Rhodococcus equi

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