Live virulent Rhodococcus equi, rather than killed or avirulent, elicits protective immunity to R. equi infection in mice

Abstract

Mice inoculated intravenously with a sublethal dose of live virulent Rhodococcus equi ATCC 33701 that contained an 85-kb virulence plasmid were immune to a lethal intravenous challenge of ATCC 33701. This immunity depended upon the dose of immunization and developed rapidly: mice primed with 10(5) live ATCC 33701 eliminated the challenged bacteria more rapidly than mice primed with doses ranging from 10(2) to 10(4) bacteria, and mice given 10(5) live ATCC 33701 intravenously withstood the lethal challenge as early as 5 days after the initial inoculation. However, this protective immunity did not develop in mice immunized with doses of heat-killed ATCC 33701 ranging from 10(6) to 10(8), or in mice immunized with doses of live ATCC 33701P-, a plasmid-cured derivative (avirulent), in doses ranging from 10(5) to 10(7). These mice had positive antibody titers against R. equi at the challenge (14 days after priming). Adoptive transfer of resistance to virulent R equi was obtained with spleen cells from mice immunized with live ATCC 33701, but not monoclonal antibody to 15- to 17-kDa virulence-associated antigens. These results revealed that live ATCC 33701P-, a plasmid-cured derivative of virulent R equi, could not elicit protective immunity, and are consistent with previous observations that protective immunity was induced by live virulent, but not killed organisms.

Pathogenicity of Rhodococcus equi in mice, isolated from environment, human and horse clinical samples

“…Many authors also suggest the presence of R. equi in inoculated animals without pathological manifestations (Multimer & Woolcock 1982, Yager et al 1991, Lazzari et al 1997. Previous investigations demonstrated R. equi lethality in immunocompetent mice (Takai et al 1999). Our data demonstrated the effect of immunodeficiency on resistance to R. equi infection in mice.…”

“…On the other hand, R. equi strains isolated form HIV reactors were virulent to immunossupressed mice independent of the presence of 85-90Kb plasmid. The majority of R. equi clinical isolates from patients with or without AIDS did not carry virulence plasmid and were avirulent to mice (Takai et al 1999).…”

“…The ability of R. equi to cause infection and death in foals and mice experimentally inoculated was related to survive and multiply within macrophages (Takai et al 1993, Madarame et al 1997, Takai et al 1999. The animals with a sound immune system did not die naturally, independently of the presence of virulence plasmids and of the bacterial number in their hepatic tissue.…”

“…Despite of the importance of R. equi disease, its pathogenesis and the singular sensibility of foals are not completely understood (Takai et al 1993, Takai et al 1999. The pathogenicity varies among strains and it is associated with the ability of R. equi to resist pulmonary and splenic clearance (Hines et al 1997, Hondalus et al 1994.…”

Rhodococcus equi -Infected Macrophages Are Recognized and Killed by CD8 + T Lymphocytes in a Major Histocompatibility Complex Class I-Unrestricted Fashion

“…Moreover, foals challenged with PC strains rapidly clear the organism without developing clinical signs or lesions. In addition, avirulent PC strains do not induce IFN-␥ responses in the lungs of immune horses, nor do they induce protective immune responses in naive, immunocompetent mice (17,45). Even SCID mice, which lack both T lymphocytes and B lymphocytes and are unable to clear virulent strains of R. equi, effectively clear a pulmonary challenge with PC strains, apparently via innate immune responses (30).…”