The potential for immunoglobulins and host defense peptides (HDPs) to reduce the use of antibiotics in animal production

Abstract

Innate defense mechanisms are aimed at quickly containing and removing infectious microorganisms and involve local stromal and immune cell activation, neutrophil recruitment and activation and the induction of host defense peptides (defensins and cathelicidins), acute phase proteins and complement activation. As an alternative to antibiotics, innate immune mechanisms are highly relevant as they offer rapid general ways to, at least partially, protect against infections and enable the build-up of a sufficient adaptive immune response. This review describes two classes of promising alternatives to antibiotics based on components of the innate host defense. First we describe immunoglobulins applied to mimic the way in which they work in the newborn as locally acting broadly active defense molecules enforcing innate immunity barriers. Secondly, the potential of host defense peptides with different modes of action, used directly, induced in situ or used as vaccine adjuvants is described.

Figure 1

The outer circle represents all infectious diseases in livestock. A large proportion of these (namely bacterial infections) can be controlled by antibiotics (grey circle). Some of those can also be controlled by alternative methods such as management measures (blue circle) and/or vaccination (yellow circle). Both of these methods can also be used to control a number of non-bacterial infections not targeted by antibiotics. A significant number of bacterial infectious diseases still remain controllable by antibiotics only, however. We suggest in this review that many of these may be controlled by non-vaccine immune methods, which, given adequate efficiency and low cost may in addition be applicable to some of the infectious diseases that can be handled by management and/or vaccination. As indicated a need for antibiotics will persist. Anyhow, presently available alternative methods can drastically reduce their total consumption and their frequency of use.

Figure 2

Trained innate immunity. Reprogramming of innate immune responses is possible by epigenetic changes induced by compounds like β-glucan. Host defense peptides (HDPs) may induce innate immune memory of monocytes and macrophages in a similar way and increase the threshold above which infection occurs [10]. Trained immunity holds promise as a new approach to decrease the need for antibiotics.

Figure 3

Transfer of maternal immunoglobulin to offspring is controlled by the interface between the maternal circulation and the placenta (or yolk sac in fish and birds). Species having an epitheliochorial interface are born without immunoglobulin in the circulation as no transfer takes place during gestation (ruminants, pigs, horses). These species are dependent on uptake of immunoglobulin from the colostrum during the first 24 h after birth and, consequently, their intestine allows immunoglobulin passage in this period, where after it closes. In species with an endotheliochorial interface, neonates have obtained a low circulatory level of immunoglobulin during gestation however are also able to take up immunoglobulins from the gut after being born and up to a week after with the majority of the uptake happening during the first 24–36 h after birth. In primates and rodents, the hemochorial placenta interface allows the neonate to be born with circulating immunoglobulins and there is therefore no perinatal uptake through the gut of maternal immunoglobulin.

Figure 4

Three-dimensional representations of structures of chicken cathelicidin-2 (CATH-2), human cathelicidin LL-37, human defensin HBD-2, xenopus magainin-2 and the immunoglobulin IgG2a. Peptide chains are colored using a color gradient ranging from blue (N-terminus) to red (C-terminus). CATH-2 consists of a double helix separated by a hinge region, LL-37 and magainin-2 adopt a continuous helical structure and HBD-2 consists of an anti-parallel β-sheet structure. The IgG2a structure consists of an Fc fragment (blue/green), two ligand-binding Fab fragments (orange/yellow/green and red/green) and bound polysaccharide ligands NAG-FUC-NAG-BMA-MAN-NAG-GAL-MAN-NAG (blue) and NAG-FUL-NAG-BMA-MAN-NAG-GAL-MAN-NAG (green).