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Avian Immune Responses to Virus Infection | 383
Polymorphonuclear leukocytes phagocytosis to enhance their capacity to clear the pathogens
Polymorphonuclear leucocytes or granulocytes are important (Bosedasgupta and Pieters, 2014). Macropinocytosis is not
host defence cells during innate immunity. Activated granulo- driven by receptor–ligand interactions and is the process of fluid
cytes use a range of effector mechanisms such as phagocytosis, engulfing, plus any fluid-phase cargo and a large part of plasma
production of a combination of toxic oxygen radicals, proteolytic membrane with its resident transmembrane molecules, particles
enzymes, myeloperoxidase, defensins, and other bactericidal or pathogens attached to them on the external face of the plasma
peptides. They also expel net-like structures of genomic DNA in membrane. An important outcome of activation of macrophages
complex with proteins such as histones, defensins, and various and DCs is the production of chemokines and cytokines that have
proteases (neutrophil extracellular traps, NETs) that trap extra- a variety of local and distant effects. The effects of IL-1β, IL-6,
cellular pathogens. The degree of activation, the release of granule TNF-α and CXCLi2 also called IL-8 or CXCL8 include activation
proteins, and generation of reactive oxygen species (ROS) all play of the vascular endothelium and increase of vascular permeability
a key role in pathogen clearance. to recruit access of effector cells, entry of immunoglobulins and
Although the contribution of neutrophils to antiviral defence activation of acute phase responses, whereas IL-12 activates NK
in mammals is not well understood, viruses can activate neu- cells and induces CD4 T-cells into Th1 cells. Viral infections espe-
trophils either by direct binding through PRRs or by binding cially induce production of interferons as described above.
through antiviral antibodies mediating ADCC. Their role has Several studies have reported that avian viruses such as IBV
been mostly studied during influenza infections and depletion of (Reddy et al., 2016), MDV (Yang et al., 2011; Chakraborty et al.,
neutrophils resulted in uncontrolled viral replication and mortal- 2017), AIV (Vervelde et al., 2013b), and ILTV (Loudovaris et al.,
ity in mice (Tumpey et al., 2005). Although beneficial for many 1991a,b) can infect macrophages and DCs. However, whether the
infections, improper and/or prolonged activation of neutrophils viruses infect a macrophage or DC directly, or whether due to the
can be detrimental and leading to severe tissue injury and organ nature of these cells they phagocytose dead virus-infected cells
disfunction (reviewed by Galani and Andreakos, 2015). In chick- remains to be elucidated. It is worth mentioning that many stud-
ens, heterophils are the equivalent of mammalian neutrophils. ies use macrophage-like cell lines such as HD11 and MQ-NCSU,
Although their role in antiviral responses has hardly been studied, which are excellent tools to study host pathogen interaction in
heterophils express PRR, including TLR3, 7, and 21, scavenger vitro but the conclusions cannot be extrapolated to the in vivo
receptors, dectin-1, and mannose receptors, suggesting that tissue resident cells.
viruses can be sensed by these cells. In avian heterophils, degranu- NK cells, macrophages, DCs and granulocytes all have unique
lation is closely associated with phagocytosis, but the content of mechanisms to combat virus-infected cells and limit viral repli-
the granules is not clearly defined (reviewed by Genovese et al., cations. Careful regulation of the innate responses is of utmost
2013). importance for controlling the balance between immunoprotec-
NK cells, monocytes and granulocytes all have unique mecha- tion and immunopathology. In addition, the ability of viruses
nisms to combat virus-infected cells and limit viral replications. to evade multiple immune pathways in parallel results in a very
Careful regulation of the innate responses is of utmost impor- complex interaction between the host and virus that can hardly
tance for controlling the balance between immunoprotection be unravelled in vivo and is difficult to control. Beside their role
and immunopathology. In addition, the ability of viruses to evade as first line of defence, the cells of the innate immune system
multiple immune pathways in parallel results in a very complex play a crucial role in the onset and steering of adaptive immune
interaction between the host and virus that can hardly be unrav- responses interacting with B and T lymphocytes.
elled in vivo and is difficult to control.
Macrophages and dendritic cells The adaptive immune system
Macrophages and DCs are amongst the key innate immune cells As for innate immunity, there is an enormous amount of infor-
that function as sentinels, strategically positioned and adapted mation determined for the adaptive immune systems of humans
for detecting, responding to and destroying foreign material. and well-studied mammalian biomedical model species. This
Their cell surfaces are designed to maximize interaction with the information is most easily accessible in a variety of excellent
environment and potential pathogens (reviewed by Stow and textbooks (Abbas et al., 2016; Murphy and Weaver, 2017; Owen
Condon, 2016). Once confronted with a pathogen or a dead cell et al., 2018). Many details of avian immune responses are also
the process of endocytosis starts. Phagocytosis is a deliberate, extensively reviewed (Schat et al., 2013).
receptor-driven process based on recognition of the pathogen and
engagement with it by receptors on cell surface. Multiple phago- Somatically diversified antigen-specific
cytic receptors are activated during the recognition of pathogens, receptors
including PPRs, opsonic receptors (immunoglobulin or comple- In contrast to innate immunity, adaptive immune systems depend
ment receptors) and apoptotic receptors (phosphatidylserine on molecules whose specificity of interaction is determined by
receptors). Once the cells have been activated by contact with variation that is constructed within different clones of somatic
pathogens, the inflammatory stimuli can reprogram the endocytic cells, each clone bearing a distinctive antigen-specific receptor.
pathway. They up-regulate receptor-independent macropinocy- For jawed vertebrates, two major lineages of lymphocytes deliver
tosis to override the less efficient process of receptor mediated adaptive immunity, T cells and B cells. T cells depend on the