Rhodococcus equi infection: Treatment and immunity in foals - DVM
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Rhodococcus equi infection: Treatment and immunity in foals
Part 2 of this series explores a foal's innate defenses against a common bacterial pneumonia and how veterinarians can enhance natural immunity.


DVM360 MAGAZINE


Opsonization

Phagocytosis is facilitated by the presence of immunoglobulins and complement known as opsonins, which function synergistically. "Adequate and partial colostrum ingestion promotes a positive effect on serum opsonization," according to the Gardner and colleagues study.2 "Complete lack of colostrum ingestion affects opsonization capacity, which was observed in the presuckle serum of control foals in comparison with post-suckle samples. Because sepsis and bacterial infection may result in consumption of opsonins, intravenous plasma transfusion becomes an important component in the treatment of neonatal foals with severe or generalized bacterial infection."2

What is opsonization? There are two major opsonins. One is complement, which is a part of the innate immune system and produced by the liver. Foals are born with low levels of complement, but these levels increase with age. The other critical opsonin is immunoglobulin. Immunoglobulin is produced by the specialized, "acquired" immune system and is either absorbed from the colostrum or produced by the foal with time.

"For a bacterium to be removed by phagocytes, the optimal condition is when it is bound either by complement or immunoglobulin, more efficiently even by both," Felippe says. "That is because phagocytes (i.e., neutrophils, macrophages, monocytes) have receptors for complement and for immunoglobulins. If a bug has an immunoglobulin associated with it, a phagocyte can bind to the immunoglobulin that is bound to it. That helps not only with internalizing the bug but also activates that cell to produce the nasty elements that will then kill the bug."

Neutrophils are very good at doing that. That's their job—to remove all these pathogens. And foal phagocytes have the benefit of functioning optimally from birth. They're also more sensitive to infection than adult phagocytes, as they possess more receptors.

But a conundrum is that the phagocytes are more efficient—and probably most efficient—when opsonins are present. "Without opsonins they are not very good," Felippe says. She goes on to say that the foal's innate immune system can function, but it's really dependent on (acquired) immunoglobulins, which are transferred through the colostrum. And if that transfer doesn't go well, sepsis is likely to occur. However, if there's only a slight environmental challenge, foals can overcome infection and do well, she says.

The Gardner and colleagues study looked at the opsonization capacity and phagocytic capacity of foals admitted to the hospital.2 The foals were divided into groups—those that had a true clinical septicemia and those that did not (sick but not systemically infected foals). There was also a control group of normal foals that were not sick.

The researchers found that phagocytic function of the foals was adequate but low when the foals arrived at the hospital, at the most critical phase of their disease, before antibiotic treatment could help them overcome the infection. The group speculated that the foals' immune systems were trying to keep up with demand and possibly sending out premature infection-fighting cells. However, once an infection is stabilized, even though the demand for an immune response is present, there is time for the cells to become mature and mount a stronger response, Felippe says.

In that transition, when they were really fighting the bugs, their phagocytic function was present but slightly lower than normal, and so was their opsonization capacity. Interestingly, their opsonization capacity was not necessarily correlated with their IgG concentrations. There seems more to it than just IgG concentrations.

"You would expect that there would be a direct association," Felippe says. "But in some foals in which there was enough IgG, opsonization capacity was still reduced in the very beginning of their hospitalization period. Once the plasma therapy and antibiotics were in place, their recovery was quite rapid."

Although IgG is the most important opsonin, other factors in serum seem to be playing a role in opsonization capacity, Felippe says. Complement has an innate dependent development. "Immediately after birth, probably with antigenic challenge, the foal makes the liver produce complement," Felippe says. And since colostrum is not a good source of complement, the foal needs to work at it. In septic foals, the rate of complement level is lower through time than in normal foals, which could be a factor of consumption.

"I would expect that complement is highly used in sepsis, so that there isn't much available circulating as there is in a normal foal," Felippe says. "Complement in concert with IgG work effectively for a robust opsonization capacity. It has opened our eyes to the fact that IgG is important; it plays a major role, but there are other things that are also important to fight certain types of organisms."

Although opsonization is important, the timing of opsonization is probably more important, Felippe says. "That should be well understood when developing strategies for protection. There have been different attempts for the use of vaccines for R. equi and protecting against it, including vaccinating the dam for a better transfer of immunoglobulins," she says. Felippe admits it's a legitimate approach but maintains that it doesn't guarantee 100 percent protection because of the factors discussed above and potential failures in adequate transfer of opsonins to the foal via colostrum. She also points out that innate immunity is dependent on elements received through passive transfer from an acquired immune system, and that both elements must be present at the right time.


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Source: DVM360 MAGAZINE,
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