在牲畜，尤其是在猪，牛和家禽农场中，使用密切相关的抗生素来防止疾病爆发和超过人类使用抗生素的数量。

Few people realize that the many antibiotics originate from only a few basic structures, such as penicillins and cephalosporins. Over decades we have grown accustomed to the luxury that our general practitioner supplies us with antibiotics when our immune system is not coping well or rapidly enough to clear an infection.

在牲畜，尤其是在猪，牛和家禽农场中，使用密切相关的抗生素来防止疾病爆发和超过人类使用抗生素的数量。在动物中使用抗生素及其在环境中的积累可能会驱动抗生素耐药性的发展。已经出现了超级细菌，对人类已知的所有抗生素有抵抗力。需要替代兽医抗生素来控制牲畜中的疾病暴发并减少抗生素的使用。

一种有希望的方法是增强动物的先天免疫系统，从而提高感染发生的阈值。这种方法的优点是，用于增强免疫系统的免疫刺激物不会直接杀死细菌。因此，不要推动抵抗力发展。在“在”期间，美国和其他人提出了使用免疫球蛋白和宿主防御肽来增强牲畜免疫系统的潜力。Second International Symposium on Alternatives to Antibiotics” in Paris, 2016 and extensively describedin a recent review inVeterinary Research.

Immunoglobulins (Igs) are antibodies that ‘label’ foreign bacteria for uptake and digestion (phagocytosis) by immune cells. Besides natural transfer and protection via breast milk, Igs can be used for passive immunization of livestock. Licensed Ig-based products are already used to protect against bacterial infections, bacterial toxins and, for instance, West Nile virus in horses.

In comparison to Igs, host defense peptides (HDPs) are small (<100 amino acids often positively charged peptides that act via multiple antimicrobial mechanisms and therefore have a low risk of inducing antimicrobial resistance). In addition to broad-spectrum antimicrobial activities (bacteria, fungi, parasites and viruses) HDPs have a capacity to modulate immune cells.

Figure 1:Host defense peptides may induce innate immune memory of monocytes and macrophages and increase the threshold above which infection occurs.

HDPs can be used in different ways. Endogenous HDP expression can be stimulated with feed additives, e.g. short-chain fatty acids or probiotics or enhanced via breed selection or transgene approaches. In addition, HDPs can be used as templates for development of new antimicrobials and immunomodulators, as vaccine adjuvants or as an adjunct to antibiotic therapies.

A prime example of the prophylactic use of HDPs in livestock to prevent infections is the ‘in ovo’ immunomodulation in poultry. In chicken,in ovoHDP treatment was shown to reduce the mortality, the number of sick birds and the severity of illness caused by a bacterial infection. Postnatal prevention with HDP-derived ‘IDRs‘ (Immune Defense Regulators) were effective against invasive and systemic bacterial infections in animal models. As an adjunct to antibiotic therapy, HDPs were shown to improve the clinical outcome in mouse models of tuberculosis, cerebral malaria and systemic bacterial infection.

Our work resulted in several patents and we continue to study the mechanisms of action of HDPs as immunomodulators and as vaccine adjuvants. In conclusion, innate host defense mechanisms offer new strategies to treat and prevent microbial infections and disease in animal husbandry.