Infectious disease is one of the major economic burdens of the equine industry. Young horses, in particular, frequently suffer from viral and bacterial infections of the respiratory tract. Rhodococcus equi is a common cause of subacute or chronic abscessating bronchopneumonia in foals less than 5 months of age. The developmental immaturity of the neonate’s immune system is considered contributory to this increased susceptibility. The neonatal period is characterized by first exposures to a vast array of potentially pathogenic microorganisms. While maternal antibodies obtained through colostrum provide some degree of protection, young animals remain at risk for infection. Vaccination of this population is thus a high priority. Unfortunately, there are a number of difficulties associated with vaccination of young animals. Maternal antibodies inhibit the development of immune responses to vaccines. Even in the absence of interfering maternal antibodies, immune responses during neonatal life are typically weak in magnitude and poorly protective.
The ability of the neonatal immune system to confer protection against viral, bacterial, and fungal infection is inadequate when compared to adults. This has been attributed to a defect in the foal’s cell-mediated immune (CMI) response. Protection against intracellular pathogens such as viruses and certain bacteria is dependent upon the generation of a CMI response. Instead of producing protective CMI responses against these agents, neonates are heavily biased toward antibody responses. Such a bias towards an antibody response has dire consequences following exposure to intracellular pathogens such as Rhodococcus equi.
What factors in the neonate are responsible for this bias are not known but could include the absence of co-stimulatory molecules necessary for the induction of a CMI response. These co-stimulatory molecules can include soluble cytokines and/or cell surface proteins that serve as co-receptors for the pathogen. Neonatal macrophages and dendritic cells have decreased expression of these co-stimulatory molecules. Since these cells play a key role in the induction of CMI responses, the absence of their co-stimulatory signals could account for the reduced CMI response in the neonate. Neonatal macrophages also produce inhibitory cytokines that can down-regulate CMI responses. This reduced expression of co-stimulatory molecules coupled with enhanced expression of inhibitory cytokines suggests these cells are intrinsically preprogrammed against the generation of CMI responses. The reason for this bias is unclear but could be the result of the maternal environment during pregnancy. Pregnant females produce factors during pregnancy that inhibit CMI responses, possibly as a means of preventing fetal rejection. These maternal influences may persist in the neonate leading to the bias against CMI responses.
What remains unclear is the process whereby the immune response eventually matures, leading to increased resistance to intracellular pathogens. Current opinion is that encounters with microbial antigens may be required for the maturation of the immune system of neonates. The precise role microbial products play is uncertain but likely involves stimulation of macrophages and dendritic cells by pathogen-associated molecular patterns (PAMPs). PAMPs are found on various bacteria and are recognized by TOLL-like receptors, or TLRs, on the macrophages and dendritic cells. These receptors are involved in the recognition of PAMPs, which leads to activation of cells and the production of various cytokines and other co-stimulatory molecules. Thus, early exposure to PAMPs could overcome the initial bias of the neonate’s immune response.
Current research efforts are directed towards understanding this process of immune maturation in the foal. The role PAMPs play in regulating the foal’s immune response is also under investigation. Information gained from these studies may enable us to develop improved therapeutics and novel approaches for increasing the resistance of foals to infectious disease.
Dr. David Horohov, (859) 257-4757, email@example.com
Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky.