A hard look at R. equi
What makes a foal susceptible to R. equi versus resistant to infection? "What we think is that the foal has a window of susceptibility for the organism to penetrate,
expand and cause disease," Felippe says.
Felippe says that one key factor in a foal's susceptibility is that R. equi has developed a mechanism that allows it to replicate itself inside macrophages—it's protected from the immune system inside
of an immune cell. R. equi also uses macrophages as a means of transportation within lung tissue.
Neutrophils are killers of R. equi if they have the opsonin, particularly immunoglobulin, that is essential for R. equi killing in neutrophils, Felippe says. How can we boost immunoglobulin? "We can give the foal hyperimmune plasma with a lot
of immunoglobulin that is against R. equi," Felippe says.
"Others have done that experimentally," she continues. "If you first give the immunoglobulin—high levels of immunoglobulin
against R. equi—to foals and then infect them, the foals control infection pretty well. They get infection. They get a little bit of pneumonia,
but they do a good job eliminating the organism and resolving disease."
But if you try to apply this in the field, the results of the studies are not as clear, according to Felippe. If specific
immunoglobulins are made available before infection, they can bind to the pathogen (opsonize it) before it enters the cell
and facilitate active phagocytosis and killing, Felippe says. And that is why some practices perform R. equi-antibody enriched plasma transfusions soon (or immediately) after birth.
Everything in this process is very dynamic. How much a mare transfers R. equi-specific immunoglobulin to a foal can be variable. "If you look in a population of horses, mare A and mare B may have a very
different antibody production, colostrum quality and transfer capability to the foal," Felippe says. "And if you would like
to even out the efficiency of immunoglobulin transfer across the foals by giving plasma transfusion, you really have to give
the plasma early, as soon as the foal is born. You have to give it before the organism gets to the airways, especially in
an environment that offers significant exposure to the organism."
But how does the Cornell team's research contribute to the understanding of the role of R. equi-specific immunoglobulins in the protection against this pathogen? Felippe says that the group's paper didn't bring any new
information about the importance of IgG.
"Studies in the 1980s showed beautifully the importance of IgG for neutrophil phagocytosis and killing of R. equi," she says. "We repeated some of those experiments to show that our model was detecting the same principles, but what our
paper additionally showed is that antibodies were containing bacterial growth extracellularly and intracellularly, suggesting
a direct interference with the bacterium. And we also showed that at least one mechanism of macrophage activation was dependent
on immunoglobulin specific against R. equi. Our study supports that immunoglobulin specific to R. equi would be beneficial, especially during the early stages of infection, in the very beginning, before the organism has established
disease, when it reaches the airways. If you focus the treatment there, there's a good chance not to develop clinical disease."
Macrophages are not good killers of R. equi, so additional immunity is needed to kill cells that are infected, i.e., cellular immunity, Felippe explains. "There have
been some studies suggesting that foals have limiting factors for their ability to kill intracellular Rhodococcus," Felippe says. "One of them is a delayed production of interferon-gamma, a cytokine produced by lymphocytes. It has been
well-documented that there is a delay in their production by the foal's immune system. However, if they were stimulated, foals
could produce interferon-gamma."