DNA Synthesis Is Activated in Mosquitoes and Human Monocytes During the Induction of Innate Immune Memory

Cime-Castillo, Jorge; Arts, Rob J. W.; Vargas, Valeria; Moreno-Torres, Ramon; Hernández‐Martínez, Salvador; Recio-Tótoro, Benito; Claudio-Piedras, Fabiola; Netea, Mihai G.; Lanz‐Mendoza, Humberto

doi:10.3389/fimmu.2018.02834

Cited by 13 publications

(10 citation statements)

References 43 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanisms behind immune priming induced from the larval stage have not been ascertained yet. Nevertheless, we have recently observed that DNA synthesis and endoreplication participates in the immune priming of adult mosquitoes against DENV and Plasmodium 6,7 . Immune priming in the Anopheles albimanus LSB-AA695BB cell line induced DNA synthesis, increasing the number of TEP and PPO1 gene-copies 7 .…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, we have recently observed that DNA synthesis and endoreplication participates in the immune priming of adult mosquitoes against DENV and Plasmodium 6,7 . Immune priming in the Anopheles albimanus LSB-AA695BB cell line induced DNA synthesis, increasing the number of TEP and PPO1 gene-copies 7 . It is noteworthy that endoreplication may also participate during immune priming in the larval stage, probably making copies of antiviral genes like AGO-2.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Immune priming with inactive dengue virus during the larval stage of Aedes aegypti protects against the infection in adult mosquitoes

Vargas

Cime-Castillo

Lanz‐Mendoza

2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Several studies have observed that the immune response in insects can be conserved, a phenomenon known as immune priming, which has been mostly tested in adult stages. However, it is unknown if induction of immune priming in larval stages protects against dengue virus (DenV) infections in adult mosquitoes. In this work, we primed larval instar 3 rd of Aedes aegypti with inactive dengue virus, producing adult mosquitoes with i) an enhanced antiviral-immune response; ii) a reduction in the load and replication of RNA of dengue virus (DENV); iii) a decline in viral infective particles production. Adult mosquitoes previously primed during larval stages over-expressed RNA interference (RNAi) markers Argonaute-2 (AGO-2) and Dicer-2 (DCR-2). We also observed inter-individual variations of DENV infection in adult mosquitoes, indicating a heterogeneous response to DENV infection in the same mosquito strain. However, mosquitoes primed during larval stages appear to control the infection, reducing the viral load. The over-expression of interferon-like factors (VAGO) and AGO-2 in the pupa stage suggests a fast activation of antiviral mechanisms after immune priming in larvae, creating a condition in which adult mosquitoes are resistant to the pathogen in the posterior exposure. Aedes aegypti is the primary vector of dengue virus (DENV). It is responsible for an estimated 390 million human infections each year 1,2. The vaccine lacking to prevent the infection in humans, and the mosquito resistance to different insecticides, make it urgent to develop new strategies to interrupt the transmission by this mosquito 3,4. Immune priming has become an important strategy to induce a protective condition against different pathogens in insects, occurring when a primary infectious exposure leads to an immune response that is enhanced upon re-exposure. This phenomenon has been described in various invertebrate taxa, including mosquitoes 3,4. Recent work by our group has analyzed the ability of Ae. aegypti to mount enhanced antiviral responses upon secondary oral DENV immune challenges. Following priming with a live or inactive virus, secondary DENV infections were shown to diminish in midguts and carcasses 5. Also, higher de novo midgut DNA synthesis was detected in challenged tissues, as determined by the incorporation of 5-bromo-2-deoxyuridine (BrDU) in DNA. Endoreplication, a type of de novo DNA synthesis, was shown to correlate with the activation of the Notch pathway, where Hindsight, Delta, and Notch were overexpressed after a secondary challenge with active DENV, in primed Ae. aegypti mosquitoes 6. These findings open a new perspective on the mechanisms underlying the vector's antiviral immune response and the effector molecules involved. Similar results have been observed in Anopheles albimanus 7 , in the LSB-AA695BB cell line (An. albimanus) and trained monocytes 8. The induction of this immune response could be difficult to carry out in the field. Therefore, it is essential to determine if we can activate the immune response in ...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immune priming with inactive dengue virus during the larval stage of Aedes aegypti protects against the infection in adult mosquitoes

Vargas

Cime-Castillo

Lanz‐Mendoza

2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nevertheless, our results indicate that such mechanisms should enable reactions that can be transferred not only within the organism (i.e., systemic reactions) but even across generations up to the F 2 . This might be helpful for narrowing down targets for further in-depth studies from the large range of candidate genes and mechanisms identified in T. castaneum (Ferro et al, 2017; Greenwood et al, 2017; Tate et al, 2017; Schulz et al, 2018) and other insect species (e.g., Castro-Vargas et al, 2017; Tassetto et al, 2017; Cime-Castillo et al, 2018; Mondotte et al, 2018). On a more cautionary note, our study also further supports the view that immune priming comprises a multitude of phenomena that might be based on diverse mechanisms among and even within species (for review see Contreras-Garduño et al, 2016; Milutinović and Kurtz, 2016).…”

Section: Discussionmentioning

confidence: 99%

Transgenerational Developmental Effects of Immune Priming in the Red Flour Beetle Tribolium castaneum

et al. 2019

View full text Add to dashboard Cite

Immune priming, the increased chance to survive a secondary encounter with a pathogen, has been described for many invertebrate species, which lack the classical adaptive immune system of vertebrates. Priming can be specific even for closely related bacterial strains, last up to the entire lifespan of an individual, and in some species, it can also be transferred to the offspring and is then called transgenerational immune priming (TGIP). In the red flour beetle Tribolium castaneum , a pest of stored grains, TGIP has even been shown to be transferred paternally after injection of adult beetles with heat-killed Bacillus thuringiensis . Here we studied whether TGIP in T. castaneum is also transferred to the second filial generation, whether it can also occur after oral and injection priming of larvae and whether it has effects on offspring development. We found that paternal priming with B. thuringiensis does not only protect the first but also the second offspring generation. Also, fitness costs of the immune priming became apparent, when the first filial generation produced fewer offspring. Furthermore, we used two different routes of exposure to prime larvae, either by injecting them with heat-killed bacteria or orally feeding them B. thuringiensis spore culture supernatant. Neither of the parental larval priming methods led to any direct benefits regarding offspring resistance. However, the injections slowed down development of the injected individuals, while oral priming with both a pathogenic and a non-pathogenic strain of B. thuringiensis delayed offspring development. The long-lasting transgenerational nature of immune priming and its impact on offspring development indicate that potentially underlying epigenetic modifications might be stable over several generations. Therefore, this form of phenotypic plasticity might impact pest control and should be considered when using products of bacterial origin against insects.

show abstract

“…Increased phagocytosis was found in silkworm ( 18 ), Drosophila ( 19 ) and Pacific oyster ( 20 ) after homologous exposure. In addition, other mechanisms such as DNA synthesis ( 21 ) and RNA methylation ( 22 ) have also been used to explain immune priming. Moreover, initial priming doses can affect the immune priming outcome.…”

Section: Introductionmentioning

confidence: 99%

The Enhanced Immune Protection in Small Abalone Haliotis diversicolor Against a Secondary Infection With Vibrio harveyi

Tuo

Bai

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

In recent years, more and more studies have shown that early pathogenic bacterial infection in invertebrates can enhance immunity and significantly reduce mortality when reinfected with the same pathogen. There are mechanisms to explain this phenomenon, but they are relatively few. In addition, dose-dependent primary infection is also associated with increased immunity. In the present study, the initial infection dose and mortality of abalone Haliotis diversicolor after reinfection with Vibrio harveyi were recorded, and the mechanism of immune enhancement was investigated by the transcriptomic response of abalone after two successive stimuli with V. harveyi. Priming with different concentrations of pathogen can enhance immunity; however, higher concentration is not always better. Compared with the first exposure, more genes were up-regulated after the second exposure. Among the commonly expressed genes, the immune related genes were significantly or persistently highly expressed after two infections and included pattern recognition receptors as well as immune effectors, such as toll-like receptors, perlucin 4, scavenger receptor class B-like protein, cytochrome P450 1B1-like, glutathione S-transferase 6, lysozyme and so on; in addition, these immune-related genes were mainly distributed in the pathways related to phagocytosis and calcium signaling. Among the specifically expressed genes, compared with the first infection, more genes were involved in the immune, metabolic and digestive pathways after the second infection, which would be more conducive to preventing the invasion of pathogens. This study outlined the mechanism of immune enhancement in abalone after secondary infection at the global molecular level, which is helpful for a comprehensive understanding of the mechanism of immune priming in invertebrates.

show abstract

DNA Synthesis Is Activated in Mosquitoes and Human Monocytes During the Induction of Innate Immune Memory

Cited by 13 publications

References 43 publications

Immune priming with inactive dengue virus during the larval stage of Aedes aegypti protects against the infection in adult mosquitoes

Immune priming with inactive dengue virus during the larval stage of Aedes aegypti protects against the infection in adult mosquitoes

Transgenerational Developmental Effects of Immune Priming in the Red Flour Beetle Tribolium castaneum

The Enhanced Immune Protection in Small Abalone Haliotis diversicolor Against a Secondary Infection With Vibrio harveyi

Contact Info

Product

Resources

About