Innate Immune Memory in Invertebrate Metazoans: A Critical Appraisal

Abstract

The ability of developing immunological memory, a characteristic feature of adaptive immunity, is clearly present also in innate immune responses. In fact, it is well known that plants and invertebrate metazoans, which only have an innate immune system, can mount a faster and more effective response upon re-exposure to a stimulus. Evidence of immune memory in invertebrates comes from studies in infection immunity, natural transplantation immunity, individual, and transgenerational immune priming. These studies strongly suggest that environment and lifestyle take part in the development of immunological memory. However, in several instances the formal correlation between the phenomenon of immune memory and molecular and functional immune parameters is still missing. In this review, we have critically examined the cellular and humoral aspects of the invertebrate immune memory responses. In particular, we have focused our analysis on studies that have addressed immune memory in the most restrictive meaning of the term, i.e., the response to a challenge of a quiescent immune system that has been primed in the past. These studies highlight the central role of an increase in the number of immune cells and of their epigenetic re-programming in the establishment of sensu stricto immune memory in invertebrates.

Transgenerational developmental effects of immune priming in the red flour beetle Tribolium castaneum

“…Over the last decade a wealth of new evidence has been put forward to demonstrate that invertebrate 37 immune systems can possess forms of immune memory and are sometimes capable of highly specific 38 responses ( Melillo et al 2018). The trigger, specificity and duration of the priming can be extremely diverse.…”

Transstadial immune activation in a mosquito: Adults that emerge from infected larvae have stronger antibacterial activity in their hemocoel yet increased susceptibility to malaria infection

“…Although transstadial immune priming may be occurring, we know that a hemocoelic bacterial infection is transstadially transmitted to the adults (Brown et al, ). Thus, we elected to instead refer to the phenotype observed here as transstadial immune activation because immune priming, in its strictest sense, involves the challenge of a quiescent immune system that has been primed in the past (Melillo et al, ).…”

“…For decades, the classical assumption was that invertebrate immune systems are not adaptive and respond identically to multiple infections (Beckage, ); however, studies on diverse groups of insects show that the innate immune system varies in response to repeated challenges (Bartholomay & Michel, ; Cooper & Eleftherianos, ; Hillyer, ; Masri & Cremer, ; Melillo, Marino, Italiani, & Boraschi, ; Milutinovic, Peuss, Ferro, & Kurtz, ; Shaw et al, ). Most notably, a prior infection can provide an insect with partial or full protection from a subsequent infection, with this increased protection being due to (a) a recall response that is faster and more powerful, (b) a shift from one type of response to another, and/or (c) a sustained immune response (Hamilton, Siva‐Jothy, & Boots, ; Melillo et al, ). Although many studies on this topic indicate that protection lasts the entirety of a single life stage, there is limited evidence that immune system activation persists across molts (Thomas & Rudolf, ).…”

JAK/STAT signaling in insect innate immunity

“…While innate immunity acts as the first line of defense among vertebrates, it is the only form of immune defense in invertebrates (Medzhitov & Janeway 2002). Due to the lack of adaptive immunity in invertebrates, the plasticity of the innate immune response confers protection against microbial invasion and pathogenesis in the host (El Chamy et al 2015;Hoffmann 2003;Melillo et al 2018).…”