Invertebrate Immunity, Natural Transplantation Immunity, Somatic and Germ Cell Parasitism, and Transposon Defense

Abstract

While the vertebrate immune system consists of innate and adaptive branches, invertebrates only have innate immunity. This feature makes them an ideal model system for studying the cellular and molecular mechanisms of innate immunity sensu stricto without reciprocal interferences from adaptive immunity. Although invertebrate immunity is evolutionarily older and a precursor of vertebrate immunity, it is far from simple. Despite lacking lymphocytes and functional immunoglobulin, the invertebrate immune system has many sophisticated mechanisms and features, such as long-term immune memory, which, for decades, have been exclusively attributed to adaptive immunity. In this review, we describe the cellular and molecular aspects of invertebrate immunity, including the epigenetic foundation of innate memory, the transgenerational inheritance of immunity, genetic immunity against invading transposons, the mechanisms of self-recognition, natural transplantation, and germ/somatic cell parasitism.

Keywords: epigenetics; hemocyte; innate immunity; innate memory; invertebrate; transgenerational inheritance; transposons.

Figure 1

Invertebrate innate immunity. PAMPs (pathogen-related molecular patterns) and DAMPs (damage-associated molecular patterns) originating from the pathogen invasion are recognized by the PPRs (pattern recognition receptors) on innate immune cells. Recognition of pathogen antigens and pathogen phagocytosis activates the immune call and induces a cascade of signaling pathways, which affect protein expression at translational and transcriptional levels. Activated immune cells produce antimicrobial factors (AMFs), such as antimicrobial peptides, oxyradicals, and melanin, which destroy pathogens. The metabolic changes in the activated immune cell can also result in the epigenetic modifications of chromatin and chromosomes. The epigenetic modifications of the genome will result in the imprinting of pathogen-encounter memory and the formation of innate memory cells. When pathogen-encounter-induced epigenetic modifications occur in gametes (usually in the egg, but sometimes also in sperm) they are transmitted to the next generation(s) where they program the innate immune cells of the offspring for rapid and strong anti-pathogen responses.

Figure 2

Pathogen melanization pathway. Recognition of pathogen antigens by immune cell receptors switches on the melanin synthesis pathway. In this pathway, the activated serine proteases convert an inactive phenol oxidase enzyme (prePO) into an active phenol oxidase (PO). The PO catalyzes the oxidation of phenols to quinones, which polymerize into melanin that is deposited on the pathogen’s surface. Eventually, a pathogen is encapsulated by the layer of melanin and killed by quinones, and reactive oxygen species are produced during the melanization process.

Figure 3

Overview of epigenetic modifications in immune-related gene expression in invertebrates. (A) Reversible histone acetylation and methylation are mediated by HATs/HDACs and HDMs/HMTs, respectively, leading to changes in chromatin structure. Histone acetylation/methylation opens chromatin structure and enables easier access to transcription machinery. Histone deacetylation/demethylation has the opposite effect, repressing gene transcription by tightening the chromatin structure. (B) LncRNAs recognize and recruit epigenetic modifiers (DNA-binding protein complexes) onto specific loci or prevent the complexes from binding (right) and introduce changes in the 3D chromatin structure. (C) RNA undergoes modification by adding chemical groups. The most common modification is M6-methyladenosine methylation. (D) DNA methylation leads to gene transcription silencing when DNA undergoes methylation at the promoter level (left panel), which blocks access to transcription factors. In contrast, the gene body part’s methylation (right panel) promotes gene expression and supports active transcription and gene elongation.