Multicellular organisms constantly encounter potentially harmful microorganisms. Although insects lack an adaptive immune system, they do have powerful means of fighting infections. Cellular responses involve phagocytosis of bacteria and encapsulation of parasites. In addition, insects can mount a humoral response against pathogens. This is characterized by the secretion of antimicrobial peptides into the hemolymph. Recognition of foreign pathogens involves specific receptors for sensing infection. These include peptidoglycan recognition proteins (PGRPs) and β‐glucan recognition proteins (βGRPs). Engagement of these receptors starts signaling pathways that activate the genes that encode antimicrobial peptides. These pathways include the Toll, the Imd, and the JAK‐STAT. This chapter describes the innate immunity of insects including both the cellular and humoral responses to bacteria, fungi, and parasites. In addition, recent advances in insect antivirus immune responses are discussed.
- innate immunity
- signal transduction
Multicellular organisms are constantly exposed to different microorganisms, many of which can be potentially harmful. To protect themselves from these microorganisms, multicellular organisms have evolved cellular and molecular defense mechanisms against infection. These defense mechanisms are known as immunity. At the beginning of an infection from viruses, bacteria, fungi, and protozoa, early mechanisms such as expression of antimicrobial products, recognition of microorganisms by pattern‐recognition receptors (PRRs), and activation of phagocytic cells get engaged for eliminating pathogens. These early mechanisms are collectively known as innate immune systems. In vertebrates, such as mammals, cells facilitate the recognition of microorganisms at later times during the course of an infection with specific receptors for microbial antigens. The T‐ and B‐lymphocytes are the cells responsible for the specific recognition of pathogenic antigens and together provide a more selective defense system, known as adaptive immunity, which provides a much better and faster response to the same pathogen during a second challenge.
Insect species live practically in every known habitat and ecological niche, except marine environments. This diversity exposes insects to all sorts of infectious agents. Yet, insects are clearly very successful organisms against infections. Although insects lack an adaptive immune system, they do have a powerful innate immune system for fighting infections. The innate immune system of insects consists of physical barriers, humoral responses, and cellular responses [1, 2].
Physical barriers include the integument and the peritrophic membrane. Integument, the outer surface of an insect, is formed by a single layer of cells covered by a multilayered cuticle . The peritrophic membrane is a layer made of chitin and glycoprotein that covers the insect midgut. It functions as a physical barrier against abrasive food particles and digestive pathogens . However, this membrane is semipermeable and therefore it is not an efficient barrier for viruses. These structures constitute the initial protection for the hemocele (the insect body cavity) and the midgut epithelium against microorganisms. When microorganisms enter these barriers, the humoral and cellular immune responses are activated. Humoral immune responses include production of antimicrobial peptides, activation of prophenoloxidase (proPO), and production of reactive oxygen species [5, 6]. Cellular immune responses include nodulation, encapsulation, and phagocytosis [7, 8].
Hemolymph, the liquid that fills the hemocele, transports nutrients throughout the insect body and also contains several types of free‐moving cells or hemocytes. There are several types of hemocytes including granulocytes, plasmatocytes, spherulocytes, and oenocytoids [7, 9]. However, it is important to emphasize that not all these hemocyte types exist in all insect species [10, 11]. Hemocytes are essential for insect immunity, as shown in
Upon infection of the hemocele, cellular immune responses are engaged almost immediately; while humoral responses take place several hours later. It is believed that invading microorganisms are first eliminated by hemocytes and later the humoral responses finish up the few microorganisms not eliminated by cells . These defense mechanisms do not work independently from each other. For example, hemocytes produce molecules that promote hemocyte‐microorganism interactions [17, 18]. These molecules function similarly to the opsonins (complement and antibodies) that increase phagocytosis of microorganisms by leukocytes . Also,
Here, I will describe insect cellular immune functions with emphasis on the innate immunity of insects including both the cellular and humoral responses to bacteria, fungi, and parasites. Specific receptors for sensing infection and the signaling pathways that activate genes for production of antimicrobial peptides will be described. In addition, recent advances in insect antivirus immune responses are discussed.
2. The inducible humoral response
One of the first identified defense mechanisms of insects is the production of antimicrobial peptides (AMPs). Upon microbial infection, a series of small peptides and proteins are produced and released into the hemolymph . The production of AMPs is highly inducible following a microbial infection, the levels of AMPs change from mostly undetectable in uninfected animals to micromolar concentrations in hemolymph of infected individuals . Expression of these AMPs comes mainly from fat‐body although hemocytes also contribute to their production [5, 22]. The first identified antimicrobial protein of insects was the lysozyme from
2.1. Antimicrobial peptides
Biochemical analysis of the hemolymph of the fruit‐fly
Insect defensins are characterized by having three or four stabilizing intramolecular disulfide bonds. The name comes from their molecular similarity to mammalian α and β defensins . Insect defensins form two groups: one with peptides presenting α‐helix/β‐sheet mixed structure and the other with peptides presenting triple‐stranded antiparallel β‐sheets. Defensins with antibacterial and antifungal activity have been reported in many Lepidopteran species [28–30].
Cecropins are small basic peptides of about 31–37 amino acid residues with an amphipathic α‐helix conformation . The first amphipathic antimicrobial peptide from insects was identified in hemolymph of the silkworm
Drosocin is a 19‐mer cationic antimicrobial peptide from
Attacins are glycine‐rich 20 kDa AMPs originally isolated from the hemolymph of
Gloverins and lebocins are also glycine‐rich AMPs found in the lepidoptera [11, 38, 39]. These peptides also inhibit bacterial growth by blocking outer‐membrane protein synthesis . In addition to their antibacterial activity, gloverins also present antifungal activity [38, 39], and recently, it has also been reported that they may have antiviral activity .
Diptericin is an AMPs rich in glycine synthesized by insects in response to a bacterial injection or to injury. It is a basic heat‐stable peptide with a molecular weight of 8.6 kDa, containing high levels of Asx, Pro, and Gly. It is active only against a limited range of Gram‐negative bacteria and seems to function by disrupting the cytoplasmic membrane of growing bacteria . Recently, diptericin has been reported to be involved not only in inhibiting bacterial growth but also in protection from oxidative stress. Authors suggested that diptericin may trap or “scavenge” free radical anions and also attenuate oxygen toxicity by increasing antioxidant enzyme activities in
Drosomycin is an inducible antifungal peptide of 44 residues initially isolated from bacteria‐challenged
Metchnikowin is a 26‐residue proline‐rich peptide whose expression in
2.2. Signaling pathways activating genes that encode antimicrobial peptides
Once a microorganism is detected by PRRs, a series of signaling molecules are activated inside cells to instruct them for different responses. These molecules follow particular signaling pathways that determine the final cellular response. In insects, the signaling pathways involved in humoral immune responses are best described in
2.2.1. The Toll pathway
The Toll pathway was initially identified as a developmental pathway
Toll signaling is activated when cleaved Spätzle binds the Toll receptor. This binding triggers dimerization of the intracytoplasmic TIR domains, inducing binding of the adaptor protein MyD88 through its own TIR domain. MyD88 binds the adaptor protein Tube, which in turn recruits the protein kinase Pelle. These interactions take place via contact of death domains in each protein. Recruitment of Pelle induces its autophosphorylation, triggering phosphorylation and degradation of cactus (an IκB inhibitor) and translocation to the nucleus of the NF‐κB transcription factors Dorsal and Dif depending on the context [51, 52, 64, 65] (Figure 2).
2.2.2. The Imd pathway
2.2.3. The JAK‐STAT pathway
As mentioned above, the Toll and Imd pathways were first described in
The canonical signaling model for the JAK‐STAT pathway indicates that after binding of a cytokine to its receptor, the receptor dimerizes and JAKs that are constitutively associated with the cytoplasmic tail of the receptor get activated. Activated JAKs phosphorylate each other and specific tyrosine residues on the cytoplasmic part of the receptor. These phosphorylated tyrosines become docking sites for the Src homology 2 (SH2) domains of STAT molecules. The STATs are then tyrosine phosphorylated by JAKs, which allows them to form dimers and translocate into the nucleus, where they bind the promoters of their target genes . In humans, this pathway is very complex due to the number of cytokines that can activate it, and the ability of the JAKs and STATs to form homo‐ and heterodimers and associate with multiple transcription factors and coactivators. There are four JAKs (JAK1, JAK2, JAK3, and TYK2) and seven STATs (STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, and STAT6) . In Drosophila, the known JAK‐STAT pathway ligands consist of only three cytokine‐like proteins called unpaired (upd), upd2, and upd3 . All three upd molecule signal via a single receptor, Domeless (Dome) , which binds to a single JAK, hopscotch (hop) , and one STAT transcription factor, Stat92E  (Figure 4). In addition, in mammals, the JAK‐STAT pathway is regulated at the receptor level by the membrane‐spanning signal transducer protein gp130 , and by negative feedback loops involving the suppressor of cytokine signaling (SOCS) proteins . In Drosophila, similar regulating mechanisms have been found. Eye transformer (ET), a no signaling protein that resembles gp130, is associated with the receptor complex, interacting with both Dome and hop. Thus, ET seems to inhibit intracellular signaling [85, 86] (Figure 4). Also, three members of the SOCS family are found in Drosophila, Socs16D, Socs36E, and Socs44A. Of these, Socs36E is the principal negative feedback loop regulator, and it is strongly induced by JAK‐STAT signaling  (Figure 4).
As described above, the humoral immune response in Drosophila is mainly controlled by the Toll and Imd pathways in cells of the fat‐body and leads to the production of antimicrobial peptides [51, 54]. Also, the JAK‐STAT pathway leads to production by the fat‐body of other proteins, including cytokines and stress response proteins. This pathway is activated by the ligand upd3. Various stress conditions, such as injury, heat‐shock, or dehydration, induce hemocytes to secrete upd3  (Figure 5). Moreover, the JAK‐STAT pathway has been shown to contribute to the Drosophila viral response. Established JAK‐STAT pathway target genes, such as TotM, upd2, and upd3, are all induced by multiple viruses . Finally, the JAK‐STAT pathway also contributes to the antimicrobial defense in the gut by inducing the expression of a subset of antimicrobial peptides, such as drosomycin‐like peptide (dro3). However, this response seems to be mediated by recognition of cell damage rather than the pathogen  (Figure 5).
3. Receptors sensing infections
Innate immune responses of insects can be triggered through the interaction of hemocyte receptors or plasma proteins with specific molecules, such as lipids or sugars, on the surface of many microorganisms . Pattern‐recognition proteins can be grouped into various types including peptidoglycan recognition protein (PGRP) , β‐1,3‐glucan recognition protein (βGRP), hemolin, and C‐type lectins.
3.1. Peptidoglycan recognition proteins (PGRPs)
Peptidoglycan recognition proteins (PGRPs) are innate immunity proteins, conserved from insects to mammals, which recognize bacterial peptidoglycan, and function in antibacterial immunity and inflammation. Mammals have four PGRPs [93, 94]. They are secreted proteins expressed in polymorphonuclear leukocytes (PGRP1), in liver (PGRP2), or in secretions (PGRP3 and PGRP4). All PGRPs recognize bacterial peptidoglycan and three of them (PGRP1, PGRP3, and PGRP4) are directly bactericidal for both Gram‐positive and Gram‐negative bacteria . Insects have up to 19 PGRPs, classified into short (S) and long (L) forms. The short forms are present in the hemolymph, cuticle, and fat‐body cells, whereas the long forms are mainly expressed in hemocytes [95, 96]. The expression of insect PGRPs is often upregulated by exposure to bacteria. These receptors activate the Toll or the Imd signal transduction pathways (described above) or induce proteolytic cascades that generate antimicrobial products [94, 97].
Known functions of PGRPs in Drosophila are as follows: the PGRP‐SA in hemolymph binds to Lys‐type peptidoglycan and together with PGRP‐SD and Gram‐negative binding protein (GNBP) 1 leads to activation of the Toll pathway (Figure 1). GNBP3 also leads to activation of the Toll pathway in response to yeast. These pattern‐recognition proteins initiate the serine protease cascades that lead to activation of the Spätzle‐processing enzyme (SPE), which in turn cleaves proSpätzle to generate free Spätzle, the ligand for Toll (Figure 1). Similarly, the Imd pathway is activated when the PGRP‐LCx homodimer complex binds DAP‐type polymeric peptidoglycan, or the heterodimer PGRP‐LCx/PGRP‐LCa binds DAP‐type monomeric peptidoglycan. PGRP‐LE can bind both polymeric and monomeric DAP‐type peptidoglycan. Extracellular PGRP‐LE activates the Imd pathway through PGRP‐LC transmembrane receptors and is also involved in activation of the prophenoloxidase (proPO) cascade upstream of the proPO‐activating enzyme (PPAE) (Figure 6). Intracellular PGRP‐LE can also activate the Imd pathway by recognizing intracellular bacteria with DAP‐type peptidoglycan and binding to the Imd adaptor protein. In addition, intracellular PGRP‐LE can activate autophagy in an Imd pathway‐independent manner (Figure 6). PGRP‐LF functions as an inhibitor of the Imd pathway, because it can bind to PGRP‐LCx but not to peptidoglycan. In this manner, it prevents the formation of a PGRP‐LC active dimer. PGRP‐LB and ‐SC1a/1b/2 cleave DAP‐type peptidoglycan to inactive fragments, thus preventing activation of the Imd pathway. In addition to its scavenger function, PGRP‐SC1a is involved in the phagocytosis of bacteria as an opsonin. PGRP‐SB1 is directly bactericidal due to its DAP‐type peptidoglycan‐specific amidase activity  (Figure 6).
3.2. Beta‐1,3‐glucan recognition proteins (βGRPs)
Insect β‐1,3‐glucan recognition proteins (βGRPs) and Gram‐negative bacteria binding proteins (GNBPs) are a family of plasma proteins with an amino‐terminal glucan‐binding domain and a carboxyl‐terminal region similar to β‐1,3‐glucanases . All β βGRPs bind to β‐1,3‐glucans on bacteria and can activate the proPO cascade.
Hemolin is a plasma protein with four immunoglobulin (Ig) domains commonly found in adhesion molecules of vertebrates . Hemolin is a common protein in several Lepidopteran species, including
3.4. C‐type lectins (CTLs)
C‐type lectins (CTLs) from animals are a large group of carbohydrate‐recognition molecules that bind ligands in a calcium‐dependent manner. Several C‐type lectins have been found in Lepidoptera including LPS‐binding protein (LBP or CTL20), immulectins ‐1, ‐2, ‐3, and ‐4, [108, 109], CTL10 , CTL11, CTL19, and CTL21 . All these lectins have two carbohydrate‐recognition domains, and their genes suggest that these types of lectins are rather unique to Lepidoptera, since they have not been found in other insect species .
Most Lepidopteran CTLs bind to bacterial LPS and some also to lipoteichoic acid [108, 109, 111], inducing agglutination of bacteria and yeast [109, 110], probably because each of the two carbohydrate‐binding domains bind to sugar residues on the surface of adjacent microbial cells . This microbial aggregation may help hemocytes eliminate pathogens via phagocytosis and nodule formation.
4. The cellular response
Cellular immune responses are immediately after an invasion of the hemocele, while humoral responses appear several hours after an infection. Hemocytes are responsible for a variety of defense responses in insects. Many variations in hemocyte immune responses exist due to the presence of millions of insect species, and we are just beginning to understand these variations [7, 112]. However, a number of frequent cellular immune responses have been described in most insects studied. These responses include nodulation, encapsulation, melanization, and phagocytosis.
There are various types of hemocytes described in insects, including granular cells, crystal cells, oenocytoids, and plasmatocytes . These hemocytes are capable of adhesion and phagocytosis . Other types of hemocytes like oenocytoids can produce proPO. This classification of hemocytes, based on morphology, does not always correlate well with cell function. Thus, other attempts have been made to classify hemocyte types. By flow cytometry, three major types of hemocytes can be separated: large granular cells, small semigranular cells, and small hyaline cells . Also, there are some monoclonal antibodies that can distinguish hemocytes based on antigenicity rather than morphology [114, 115]. A number of those monoclonal antibodies could also inhibit some cellular responses [116, 117]. In
Crystal cells are relatively large cells with crystalline inclusions, thus their name. They produce the zymogen proPO, which is activated during melanization. Melanin deposits are important for wound healing or encapsulation of parasites [119, 120]. Plasmatocytes comprise approximately 95% of the hemocyte pool. They are rather small cells (around 10 μm in diameter), but extend large lamellipodial protrusions and form dynamic filopodia [121, 122]. Plasmatocytes are long‐lived cells that seem to persist through the entire life of a fly . Mature plasmatocytes express Croquemort (Crq), a CD36 scavenger receptor ortholog, Peroxidasin, an extracellular matrix enzyme, and phagocytic receptors . Lamellocytes are flat cells that appear during larval stages and only detectable when the larvae is infected by parasitic organisms. These hemocytes are mainly responsible for encapsulating the parasitoid wasp egg . Lamellocytes seem to differentiate from a precursor pool of plasmatocytes , during a wasp egg infestation and also during sterile injury [125, 126] (Figure 7).
Independently of the type of hemocyte involved, insect immune responses initiate with adhesion of granular hemocytes and plasmatocytes to foreign surfaces or to other cells [127, 128]. Adhesion of hemocytes leads to phagocytosis and also to nodule formation and encapsulation. These cellular innate functions are described next.
Phagocytosis is the process by which cells recognize, bind, and ingest relatively large particles . In insects, phagocytosis is performed by a subset of hemocytes in the hemolymph . Professional phagocytes in Diptera and Lepidoptera have been described as plasmatocytes and granular hemocytes, respectively . In agreement with this, plasmatocytes or granulocytes are the main phagocytic cells in most insects [7, 113, 130, 131]. Recognition of target particles for phagocytosis can be direct by specific cell‐surface receptors, or indirect by opsonins that cover the particle so that it can be detected by phagocytic receptors. During development, phagocytic hemocytes eliminate many dying cells, which are detected by the scavenger receptors Croquemort , and Draper . In the embryo, hemocytes phagocyte live bacteria but the receptors involved have not been yet identified . In the larva and adult insects, recognition of microorganisms is mediated by the Nimrod family receptors Eater  and NimC1 , which bind to both Gram‐positive and Gram‐negative bacteria. Cytokines capable of activating hemocyte functions have also been reported in Lepidoptera insects. A hemocyte chemotactic peptide from
When the initial phagocytic immune response is not sufficient, hemocytes activate other mechanisms to control infections. To deal with large bacterial loads, hemocytes form nodules to control the infections. Nodulation involves the formation of multicellular hemocyte aggregates that entrap large numbers of bacteria. First, hemocytes surround bacteria and then join other hemocytes to form small aggregates. These cell aggregates continue growing by adding more hemocytes until large nodules are formed. At the end, the nodule is covered with layers of flattened hemocytes and it is melanized. Melanin‐covered nodules efficiently isolate bacteria from the hemolymph. Although the process of nodule formation is not completely characterized, certain molecules such as eicosanoids, proPO, and dopa decarboxylase (Ddc) are important for nodule formation in many insect species [139–142]. In addition, screenings for novel immune genes from an Indian saturniid silkmoth (
For larger pathogens such as parasites, protozoa, and nematodes, hemocytes respond by forming a capsule around the foreign organism. Lamellocytes are the effector cells of encapsulation. Lamellocytes bind to the target in multiple cell layers until they form a capsule around the invader. The capsule is normally melanized at the end by degranulation of crystal cells . Inside the capsule the invading organism is killed by reactive cytotoxic products or by asphyxia . Insect hemocytes aggregate in multiple layers during encapsulation and bind to microorganisms during phagocytosis. These functions can be mediated by integrins  and indeed various integrins have been found in insect hemocytes . Integrins are also relevant for encapsulation. Various α and β integrins are required for microbial recognition by
Interestingly, recent reports have shown that insect hemocytes can release chromatin in a controlled manner to form extracellular traps , similar to the NETs formed by mammalian neutrophils [151, 152]. Hemocytes release their nucleic acids in a process known as ETosis. The chromatin fibers participate in histone‐mediated killing of microorganisms , and also in the process of encapsulation by creating a scaffold on which hemocytes can assemble .
Melanization is the process of melanin formation. It is activated during wound healing and also in nodule and capsule formation against large pathogens or parasites in several insects [8, 154]. The enzyme phenoloxidase (PO) is a key in this process. Activation of proPO to PO  is mediated by a Serine proteinase cascade  and requires pattern‐recognition proteins such as PGRP or βGRP. Then active PO binds to foreign surfaces including hemocyte membranes , where it initiates melanin formation. PO acts on tyrosine and converts it to dopa . Dopa can then be decarboxylated by Ddc to dopamine or further oxidized by PO to dopaquinone. Both products are then further metabolized to eumelanin and finally melanin .
5. Antivirus insect response
Insects, like any other organism, are also infected by viruses. Some viruses are restricted to insect cells and are pathogenic to them; other viruses are transmitted to mammals by biting insects. Understanding the insect innate immune response against viruses thus has tremendous medical and economic importance.
The major mechanism of antiviral defense is the RNA interference (RNAi) pathway that recognizes virus‐derived double‐stranded RNA (dsRNA) to produce small, interfering RNAs (siRNAs). These siRNAs, in turn, target viral RNA for degradation and hence suppress virus replication. In addition, other innate antimicrobial pathways such as Imd, Toll, and JAK‐STAT pathways have also been shown to play important roles in insect antiviral responses. In particular, the JAK‐STAT pathway seems to function similarly to the mammalian interferon system. A virus‐infected cell sends a signal that activates this pathway in uninfected bystander cells leading to antiviral activity. Finally, the autophagy pathway has also been suggested to be important in some viral infections.
5.1. The RNA interference (RNAi) pathway
When challenged with viruses, the most robust insect response is through the RNA interference (RNAi) pathway (Figure 8). Double‐stranded viral RNA is detected by Dicer‐2 (a member of the RNase III family of endoribonucleases) together with the protein R2D2 [158, 159]. Then, Dicer‐2 cleaves the dsRNA into small (21‐nucleotide) duplex DNA fragments [160, 161]. Unwinding of the duplex takes place and a guide strand is selected on the basis of complementarity. The siRNA guide strand is then loaded into the RNA‐induced silencing complex (RISC), which includes the RNase Argonaute . A target viral RNA pairs with the guide strand, and it is degraded by Argonaut (Figure 8).
The importance of the RNAi pathway for controlling virus infections is highlighted by the fact that several viruses have been found to produce RNAi suppressor proteins (1A proteins in Nodaviridae, or B2 proteins in Dicistroviridae) that block the action of the RISC during infection [163, 164]. The B2 protein from the flock house virus (FHV) is a dimer that binds to dsRNA and prevents the cleavage of dsRNA by Dicer‐2 . The A1 protein from Drosophila C virus (DCV) functions similarly to FHV B2, by binding to dsRNA and preventing cleavage . In contrast, the 1A protein of cricket paralysis virus (CrPV) interacts with Argonaute and inhibits its RNAse activity  (Figure 8). When viruses do not have these proteins they replicate poorly and the insect is able to clear the infection completely. The RNAi pathway is clearly very important also for protecting mammalian cells against viruses. Recently, the NS4B protein of dengue virus 2 (DENV‐2), flavivirus was found to inhibit the siRNA pathways both in mammalian and insect (Sf21) cells .
5.2. The JAK‐STAT pathway
In addition to the RNAi pathway, the Toll [167, 168] and Imd signaling [169, 170] pathways have been also reported to be involved in antivirus responses. In addition to AMPs, these pathways induce particular sets of genes that are distinct from the genes induced by bacteria or fungi, depending on the virus involved . The actual mechanism for virus recognition and the particular response induced through these pathways is just beginning to be elucidated. In contrast, the JAK‐STAT pathway response to viruses seems to be more relevant for preventing the spread of infection . Recent reports also suggest that the JAK‐STAT pathway may function similarly to the mammalian interferon system . Infected cells produce factors that activate this pathway in uninfected bystander cells inducing an antiviral state in those cells [172, 173].
As mentioned earlier, the JAK‐STAT pathway was initially characterized for its role in development and hemocyte proliferation . The JAK‐STAT pathway also gets activated in respond to bacterial infections leading to production of AMPs and other effector molecules [55, 174]. This pathway is activated in a paracrine fashion through the binding of secreted ligands. In the case of virus infections, a novel ligand for the JAK‐STAT pathway has recently been identified. In fruit flies, DCV and Sindbis virus (SINV) infections result in increased expression of mRNA for Vago, an 18 kDa cysteine‐rich protein with a single von Willebrand factor type C motif . Vago was then shown to be secreted by West Nile virus (WNV)‐infected
5.3. The autophagy pathway
Autophagy has also been proposed as another antiviral mechanism in insects that is independent of the Toll, Imd, or JAK‐STAT pathways [177, 178]. Autophagy is the process by which double‐membrane vesicles named autophagosomes are formed inside cells. These vesicles are formed with newly synthesized membranes that incorporate large cytoplasmic components including damaged organelles or protein aggregates. Then, the autophagosome fuses with lysosomes and degrades its content. Autophagy is induced by several stress signals including nutrient starvation, infection, and cellular repair mechanisms. In this manner, the degradative process of autophagy helps recycle nutrients and maintains cellular homeostasis . The signaling pathway to autophagy involves the phosphoinositide 3‐kinase (PI3K)‐Akt pathway, which augments the level of TOR, a negative regulator of autophagy  (Figure 10). During growing conditions, TOR is active and phosphorylates Autophagy‐related (Atg) 13 protein at multiple sites. This prevents Atg13 to bind with Atg1, a central regulator for autophagy , leading to decreased Atg1 kinase activity and blocking autophagy (Figure 10). During starvation conditions, TOR activity is reduced and Atg13 is rapidly dephosphorylated and forms a complex with Atg1, thus activating it. Atg1 in turn binds to other Atg proteins for assembly of the preautophagosomal structure (PAS) leading to autophagy (Figure 10). Different Atg proteins accumulate at the PAS under normal growing conditions to generate cytoplasm to vacuole targeting (Cvt) vesicles, or under starvation conditions to generate autophagosomes .
In an infection of
Insects clearly possess powerful defense mechanisms for fighting infections. Cellular responses involve phagocytosis of bacteria, and encapsulation of parasites, while humoral responses involve secretion of antimicrobial peptides into the hemolymph. Recognition of foreign pathogens involves specific receptors such as peptidoglycan recognition proteins (PGRPs), β‐glucan recognition proteins (βGRPs), and Toll‐related proteins. These receptors activate signaling pathways such as the Toll, the Imd, and the JAK‐STAT pathways. The particular pathway activated by each pathogen and the final outcome in each case are still not completely known. This is particularly true for viral infections. Thus, future research in the area of insect immunity promises to be full of surprises.
Another fascinating aspect of insect defense mechanisms against infections is the current view that insects depend only on its innate immune response to fight invading microorganisms. By definition, innate immunity lacks adaptive characteristics. However, there are some reports showing that in
Finally, most of what we know about insect innate immunity comes from studies of
This work was supported by grant 254434 from Consejo Nacional de Ciencia y Tecnología, Mexico.
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