Bharat Bhusan Patnaik
Yong Seok Lee
Yeon Soo Han3- 1Department of Biosciences and Biotechnology, Fakir Mohan University, Balasore, India
- 2Department of Biology, College of Natural Sciences, Soonchunhyang University, Asan, South Korea
- 3Department of Applied Biology, Institute of Environmentally-Friendly Agriculture, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, South Korea
Editorial on the Research Topic
Innate Immune System Guiding Physiological Plasticity in Invertebrates
Innate immunity mechanisms have provided an effective means of surveillance and protection against parasites and pathogens in invertebrates. With the lack of adaptive immunity, invertebrates rely on the plasticity conferred by innate immunity to eliminate pathogens, and perhaps more importantly discriminating them from other microorganisms. Moreover, credible evidences from studies in infection immunity, transplantation immunity, individual, and transgenerational immune priming have highlighted the development of immunological memory, a characteristic feature of adaptive immunity, under the innate immune response specialty of invertebrates. This Research Topic gathers different contributions highlighting the phenotypic plasticity in terms of innate immunity traits underlying the physiological status of invertebrates. These contributions expand our understanding of the novel components of innate immunity signaling cascades, elucidation of physiological fitness traits and pathogen evasion mechanisms intricately attributed to invertebrate survival.
The mealworm beetle, Tenebrio molitor has provided rich insights to unravel the mysteries of innate immune mechanisms in invertebrates pertinent to host-pathogen interactions. In the last decade or so, many critical components of Toll, Imd, Jak-Stat, and autophagy signaling cascades have been deciphered in the beetle model using elegant biochemical, genetic, and genomics approaches. These studies have collectively highlighted antimicrobial innate immune responses in T. molitor while characterizing the conserved pathway components regarding antimicrobial peptide (AMP) production. The first article of this Research Topic (Bae et al.) discusses the anti-Gram-negative function of another Toll ligand spätzle 1b (TmSpz1b) identified from the RNA sequencing database of T. molitor. Other studies, reported by the same research group, have critically characterized the function of T. molitor spätzle isoforms such as spätzle 5 (TmSpz5) and spätzle 6 (TmSpz6) in regulating AMP production in the Malpighian tubules in response to Escherichia coli, and against E. coli and Staphylococcus aureus, respectively (Edosa et al., 2020; Ali Mohammadie Kojour et al., 2021). TmSpz1b was characterized as a secretory protein with a conserved cystine-knot domain as evidenced in other insects including spätzle protein in Drosophila melanogaster. Further, the authors reported the requirement of TmSpz1b in regulation of AMP genes in hemocytes and fat bodies and showing susceptible phenotype against E. coli infection. The inclusion of TmSpz1b in regulating Toll pathway was suggested as TmSpz1b silenced individuals showed downregulation of TmDorsal (a critical NF-kB factor regulating Toll cascade mechanisms) transcripts. In the second article, Ko et al. functionally characterized the inhibitor of nuclear factor kappa B kinase epsilon isoform from T. molitor (TmIKKε), that is a transcriptional regulator of Imd pathway and Janus kinase (JNK) activation and apoptosis (downstream of Imd) pathway mediated by the phosphorylation of DIAP1 as evidenced from studies involving D. melanogaster IKKε. Further, they suggested the putative involvement of TmIKKε in conferring immunity against E. coli infection. Interestingly, in gut the Toll NF-kB factors TmDorX1 and TmDorX2 were downregulated in TmIKKε-silenced individuals suggesting systemic immunity in gut mediated by the Toll pathway. However, in an earlier study, TmIKKγ-silenced individuals showed less TmRelish (NF-kB transcription factor of Imd pathway) transcript abundance highlighting antimicrobial innate immune response mediated by Imd pathway (Ko et al., 2020).
Regarding host-pathogen interactions, another contribution by Wronska et al. has discussed apoptosis (changes in caspase activity) as an integral component of innate immune system particularly in the context of entomopathogenic fungus Conidiobolus coronatus infection of greater wax moth, Galleria mellonella. Hypothetically, the authors assumed that in immunocompetent insect hemocytes, fungal infection stimulates apoptosis and influences eicosanoid levels, largely synthesized by cyclooxygenase (COXs), lipoxygenase (LOX) as well as the cytochrome P450 pathway. Significant increase in phospholipase A2 (PLA2) activity in the infected larval hemolymph acted as a biomarker for eicosanoid biosynthesis and correlated well to a rise in general activity of caspases and prostaglandins. Hence, immunity in insects under the challenge of fungal infection creates new directions to study the apoptotic phenomenon regulated by not only caspases but also by other factors such as eicosanoids. It would also be interesting to correlate the activation of PLA2 with gene activation of AMPs in Dorsal- and Relish-silenced insect larvae to suggest the requirement of Toll/Imd signal pathways for eicosanoid biosynthesis. It has been reported that the eicosanoid mediating innate immune responses in insects are functionally linked to Toll/Imd signal pathways in the beet armyworm, Spodoptera exigua and in the red flour beetle, Tribolium castaneum (Shrestha and Kim 2010; Park and Kim 2012), providing compelling evidence for including PLA2 activity and caspase-mediated apoptosis as an efficient immune surveillance mechanism against pathogenic infections in insects.
The physiological capacity to actively metabolize uric acid thus limiting Plasmodium parasite survival was addressed in Kwon and Smith, by analyzing both urate oxidase (UO) and allatoicase (ALLC) expression by qRT-PCR and RNAi. The authors suggested that the mosquito host manipulates uric acid metabolism to limit pathogenic infections. This was demonstrated by silencing UO (metabolism of uric acid to urea) in mosquito host, that resulted in increased uric acid levels, enhancing parasite survival. Hence, it was substantiated from the study that integral to vectorial capacity (mosquito vector competence) is the nitrogen metabolism pathway. Earlier studies in Drosophila host (under bacterial challenge) and in tsetse flies (under Trypanosoma brucei infection) have also supported the hypothesis that uric acid promotes the success of parasitic and pathogenic infections (MacLeod et al., 2007; Lang et al., 2019).
The phenomenon of “immune priming” was evaluated by Hidalgo and Armitage by infecting D. melanogaster with one of the two bacterial species, Lactococcus lactis or Providencia burhodogranariea (either heat-killed or inactivated with formaldehyde). To the surprise of the authors and in contrast to previous reports on immune priming in insects, primary exposure treatments did not provide a survival benefit to pathogen-challenged host suggesting that immune priming is not a ubiquitous phenomenon in insect immunity and may require specific circumstances to occur. The dynamic nature of host resistance over the infection course was also suggested as pre-exposed flies showed resistance that varied over the course of infection. The pre-exposure advantage on a secondary challenge was nullified in the study contemplating future studies to understand adaptive value of this phenomenon considering specific host-pathogen combinations. As discussed in a previous report, the pronounced immune priming phenomenon in industrial insects such as T. molitor could be crucial to obtain sustainable stocks of insect population for multiplication as food (Ali Mohammadie Kojour et al., 2022).
We hope that the readers of this Research Topic would use this resource as a useful reference tool while advancing their research directions towards intricacies of innate immune response in host-pathogen interactions.
Author Contributions
BP wrote the first draft. YL, YH, and YJ provided critical comments. All the authors agreed on the submitted version.
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s Note
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Acknowledgments
The authors acknowledge the funding received from the National Research Foundation, Korea (NRF-2021R1A6A1A03039503/NRF-2017R1D1A3B06034971) and the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) through Agricultural Machinery/Equipment Localization Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (No. 321055-05). Further, the authors acknowledge the support received from the Agreement of Cooperation between Fakir Mohan University, Balasore, India and Department of Biology, Soonchunhyang University, Asan, Korea/Department of Applied Biology, Chonnam National University, Gwangju, Korea.
References
Ali Mohammadie Kojour M., Baliarsingh S., Jang H. A., Yun K., Park K. B., Lee J. E., et al. (2022). Current Knowledge of Immune Priming in Invertebrates, Emphasizing Studies on Tenebrio molitor. Dev. Comp. Immunol. 127, 104284. doi:10.1016/j.dci.2021.104284
Ali Mohammadie Kojour M., Edosa T. T., Jang H. A., Keshavarz M., Jo Y. H., Han Y. S. (2021). Critical Roles of Spätzle5 in Antimicrobial Peptide Production against Escherichia coli in Tenebrio molitor Malpighian Tubules. Front. Immunol. 12, 760475. doi:10.3389/fimmu.2021.760475
Edosa T. T., Jo Y. H., Keshavarz M., Bae Y. M., Kim D. H., Lee Y. S., et al. (2020). TmSpz6 Is Essential for Regulating the Immune Response to Escherichia coli and Staphylococcus aureus Infection in Tenebrio molitor. Insects 11, 105. doi:10.3390/insects11020105
Ko H. J., Jo Y. H., Patnaik B. B., Park K. B., Kim C. E., Keshavarz M., et al. (2020). IKKγ/NEMO Is Required to Confer Antimicrobial Innate Immune Responses in the Yellow Mealworm, Tenebrio Molitor. Ijms 21, 6734. doi:10.3390/ijms21186734
Lang S., Hilsabeck T. A., Wilson K. A., Sharma A., Bose N., Brackman D. J., et al. (2019). A Conserved Role of the Insulin-like Signaling Pathway in Diet-dependent Uric Acid Pathologies in Drosophila melanogaster. PLoS Genet. 15, e1008318. doi:10.1371/journal.pgen.1008318
MacLeod E. T., Maudlin I., Darby A. C., Welburn S. C. (2007). Antioxidants Promote Establishment of Trypanosome Infections in Tsetse. Parasitology 134, 827–831. doi:10.1017/S0031182007002247
Park J.-A., Kim Y. (2012). Eicosanoid Biosynthesis Is Activated via Toll, but Not Imd Signal Pathway in Response to Fungal Infection. J. Invertebr. Pathology 110, 382–388. doi:10.1016/j.jip.2012.04.015
Keywords: innate immunity, Tenebrio molitor, immune priming, physiological plasticity, host-pathogen interaction
Citation: Patnaik BB, Lee YS, Han YS and Jo YH (2022) Editorial: Innate Immune System Guiding Physiological Plasticity in Invertebrates. Front. Physiol. 13:947707. doi: 10.3389/fphys.2022.947707
Received: 19 May 2022; Accepted: 23 May 2022;
Published: 14 June 2022.
Edited and reviewed by:
Klaus H. Hoffmann, University of Bayreuth, GermanyCopyright © 2022 Patnaik, Lee, Han and Jo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Bharat Bhusan Patnaik, ZHJiaGFyYXRiaHVzYW40QGdtYWlsLmNvbQ==