Why is interferon-gamma so important? For at least two reasons: "One is that it activates cellular immunity against intracellular
pathogens," Felippe says. "Secondly, it activates a more efficient killing system in the macrophages that not only uses oxygen
reactive elements, but also nitrogen reactive elements. The two together produce peroxynitrite, which is effective in killing
Rhodococcus. But without both, Rhodococcus is not as effectively eliminated. This activation is primarily interferon-gamma induced, and at some level TNF-alpha induced."
In early life, a foal may not have the ability to prevent the disease and fight the infection—that creates the window of susceptibility
and allows the disease. After foals are stimulated with infection, they create this immune response, but it still takes time
for them to fight the infection and control disease.
"In fact, we now realize, clinically, that a lot of foals acquire Rhodococcus infection and they manage their disease without antibiotic therapy," Felippe says. "With age, they are capable of eliminating
the infection without antibiotics. In the field, it is becoming common practice to monitor the disease, monitor the foals
and only give antibiotics when the disease becomes overwhelming. It is an interesting understanding about the development
of the immune response in the foal."
So how is this stimulation occurring in the airways? "Ute Schwab in our lab created an in vitro system with respiratory epithelial
cells of the horse, and she studied the dynamics between the signaling of the epithelial cells and phagocytes in the presence
of R. equi," Felippe says.3 "It is beautiful how activation can control infection and how there is a difference between foal macrophages and adult macrophages
in this process. So we believe that the airway epithelium signals the presence of R. equi in the environment, attracts and activates resident macrophages, and subsequently neutrophils. It is very possible that,
when neutrophils arrive to the airways with appropriate concentration of R. equi-specific immunoglobulin, Rhodococcus removal is efficient and disease can be prevented. Using this system, we also want to learn more about how the adult horse
airway epithelium activates macrophages—if that capacity differs from the foal airway epithelium and how that affects R. equi survival."
Many factors are at play in a foal's immunity—from the efficiency of transfer of immunoglobulins and proinflammatory cytokines
to the foal via colostrum, the physiologic developmental phases of the immune system, and a foal's ability to respond to antigens,
as covered in part 1 of this series, to the timing of presence of essential opsonization to fight R. equi infections in the airways. Further research will continue to illuminate ways practitioners can better foster the health of
Ed Kane, PhD, is a researcher and consultant in animal nutrition. He is an author and editor on nutrition, physiology and
veterinary medicine with a background in horses, pets and livestock. Kane is based in Seattle.
1. Dawson DR, Nydam DV, Price CT, et al. Effects of opsonization of Rhodococcus equi on bacterial viability and phagocyte activation. Am J Vet Res 2011;72(11):1465-1475.
2. Gardner RB, Nydam DV, Luna JA, et al. Serum opsonization capacity, phagocytosis, and oxidative burst activity in neonatal
foals in the intensive care unit. J Vet Intern Med 2007;21(4):797-805.
3. Schwab U, Caldwell S, Matychak MB, et al. A 3-D airway epithelial cell and macrophage co-culture system to study Rhodococcus equi infection. J Vet Immunol Immunopathol 2013; in press (ePub available).