1. Introduction

Chicken production plays a vital role in meeting the increasing demand for chicken products (such as meat and eggs) by using adequate management practices and structured breeding programs [1]. Despite the improvement in poultry management practices, bacterial disease is still a big threat to the chicken production industry ^[1][2][3][1,2,3]. For instance, countries like United States of America, China, Southern Europe and Portugal accounted for up to 50% loss in poultry product due to bacterial infections ^[2][3][2,3]. This problem has led to the incessant use of antibiotics due to their ability to improve feed efficiency, weight and poultry health. However, the use of antibiotics has been found to cause the emergence of antimicrobial resistant genes in chickens [3]. These antimicrobial resistant genes are then transferred between bacteria in the environment and into human pathogens ^[2][3][2,3] thereby causing serious health issues. For this reason, antibiotic use for growth promotion has been banned in some countries. Froebel et al. [4] stated that some government policies such as the United States Veterinary Feed Directive and the European Union are discouraging use of antibiotic growth promoters. There is, therefore, an urgent need to find alternative measures to manage bacterial diseases without compromising the health of chickens, humans or the environment.

The defense mechanism of chickens against pathogenic diseases entails the activity of both the innate and adaptive immune systems. Bacterial diseases are combated by an innate immune system (IIS) before the intervention of the adaptive immune system ^[5][6][7][5,6,7]. The IIS response is the host’s first line defense mechanism against any microbial infection; it functions by fighting pathogens at the point of entry via both innate immune cells and innate immune proteins ^[8][9][8,9]. On the other hand, the adaptive immune system ensures protection against subsequent infections by the action of both T and B lymphocytes [10] with activity against specific pathogens.

2. Brief Overview of the Chicken Innate Immune System

The IIS response is the host’s first line defense mechanism against microbial infection. For example, it functions by fighting pathogens at the point of entry via both innate immune cells and secreted soluble effector proteins [9]. The main innate immune cells include phagocytes such as macrophages and heterophils (comparable to the mammalian neutrophils), but also epithelial cells play an important role in the immediate response towards invading pathogens. The specific innate immune proteins are multiple and include complement system proteins, cytokines and chemokines (often secreted by the innate immune cells) and secreted soluble effector proteins, such as collectins and antimicrobial peptides, that can also kill or neutralize microbes [9].

An important first step in the innate immune response is recognition of the pathogen. There are specific structures on the microbe called pathogen-associated molecular patterns (PAMPs) which are recognized by membrane bound, or soluble pattern recognition receptors (PRRs) of the host. Larsen et al. [11] and Faghfouri et al. [12], both showed that toll-like receptors (TLRs), retinoic acid-inducible gene-I-like receptors (RLRs) and C-type lectin receptors (CLRs) are an important group of PRRs that can recognize PAMPs from microbial DNA/RNA to protein and membrane components of microbes. When PAMPs bind to PRRs, it leads to a signaling cascade which in turn increases cytokine and chemokine production; these molecules can activate immune cells. In some cases, through chemotaxis, the numbers of immune cells are increased at the site of infection. Signaling can also increase the production and secretion of antimicrobial compounds, such as defensins or other antimicrobial proteins that can neutralize the pathogens ^[13][14][13,14].

3. Mannose-Binding Lectin

Mannose-binding lectin (MBL) is also considered a member of the PRR family. In contrast to other PRRs such as TLRs, it is not membrane bound but a soluble-type protein which can also be considered as an effector molecule. Binding of MBL to PAMPs on the pathogen cell wall can initiate the lectin pathway of complement activation, which further neutralizes pathogens by aggregating them, (denying attachment of bacteria to epithelial cells of host). MBL can also bind apoptotic cells via ligation (joining of two DNA strands by a phosphate ester linkage) on the phagocyte membrane by macrophages [15]. The removal of apoptotic cells is necessary for organogenesis, tissue maintenance and proper activity of the immune system. MBL is also regarded as an acute-phase protein (proteins which respond to inflammatory signals by increasing its plasma concentration by 25% or more). These proteins participate in host defense and adaptation and also act as transport proteins with antioxidant activity ^[15][16][15,16]. Mannose-binding lectin is an innate host defense molecule, with great affinity to initiate the lectin pathway of complement via attached mannose-binding lectin-associated serine protease (MASP-2) ^[17][18][19][17,18,19]. The MBL structure provides a wide array of defenses against pathogens’ physiochemical activities as mentioned in the study of Takahashi [7]. Several authors have indeed discussed the impact of MBL on bacterial infection in chickens ^{[15][16][17][18]}[15,16,17,18].

4. Complement System

The complement system (CS) plays a very important role in defending the host against diseases and inflammation. It is known that the CS consists of more than 30 soluble or membrane proteins that upon activation interact (the complement cascade), eventually leading to formation of an antibacterial complex of proteins and formation of several signaling molecules that stimulate further immune responses (Figure 1) ^[6][20][6,31].

Figure 1. Outline of the major components and mode of action of the complement system.

The order of events of the complement cascade is as follows: Firstly, the complement cascade is activated via one of three different but eventually merging pathways: the lectin pathway, the classical pathway and the alternative pathway ^{[6][20][21][22][23][24]}[6,31,32,33,34,35]. These pathways bring forth the formation of convertase enzymes which form several chemokine and other important signaling factors including the complement factor (C5b).

All these pathways converge at C3, which is the most abundant complement protein found in the blood. At the point of converging, there is a formation of activation products such as C3a, C3b, C5a and the MAC or C5b-9 (Figure 1). The membrane attack complex (MAC) is a protein complex that can bind and lyse Gram-negative bacteria. It becomes triggered within a few minutes upon entry of Gram-negative bacteria in the host cells ^[20][25][31,36]. More details on how the complement system functions can be further seen in excellent reviews of Sarma and Ward, [6] and Heesterbeek et al. ^[26][37].