Development of immunity in basal metazoans

Dr Mauricio Rodriguez-Lanetty from Florida International University (FIU), is currently conducting research that focuses on immunological priming in corals and anemones, a process by which an animal can resist pathogens through repeated, non-lethal exposure. As corals are at risk due to climate change, this is an important project to help further our understanding of their immunology. The project also includes an outreach programme to motivate minority students to pursue science as a career.

Coral reefs are one of the most important ecosystems on the planet as they support a wide and diverse array of organisms and human activities. Unfortunately, however, they are also one of the most vulnerable.

Corals are categorised as anthozoans, a class shared by anemones, and are made up of small, colonial animals which come together to create reefs. As coral tissues contain symbiotic algae, they can only live within a “goldilocks zone”, where the waters are suitably warm and where the algae receive enough light to photosynthesise and support their coralline hosts. Climate change has reduced the size of the area habitable by corals due to ocean warming, and has caused further issues that include ocean acidification and an increased prevalence of coral diseases. As such, swathes of reef are being lost around the world due to bleaching (when symbiotic algae leave their coral host).

It is imperative that we find ways to improve corals’ resilience against worsening environmental conditions and the range of problems they can cause. Dr Mauricio Rodriguez-Lanetty is currently leading a programme to research immunological priming in anthozoans and determine if these animals can be inoculated against disease. His programme will also provide educational and research experiences to high school, undergraduate, and postgraduate students to inspire the next generation of scientists.

Coral disease
Not only are corals very visually appealing, attracting thousands of tourists every year, they provide numerous services to local populations. They act as nurseries for fish, support fisheries, and protect coastlines from facing the full force of storms. They are also home to thousands of animals and are areas of high biodiversity. As such, it is vital that we find ways to protect them against the changing environment.

Anemones exposed to the pathogen twice were more likely to survive future encounters to it than those naïve to it

One recent problem faced by corals is the prevalence of pathogens, which has been exacerbated by climate change. As corals are very long-lived (some can survive for hundreds of years), it is expected that they will encounter the same pathogens at several points during their lives. Therefore, it is believed that, through repeated low-level exposure, corals may build up a resistance against disease-causing pathogens. However, this area of science is highly under-researched.

Anemones as models
To further our understanding of disease resistance in corals, Dr Rodriguez-Lanetty studies the immune response of anemones as a model system. Anemones are easier to cultivate in laboratories, where they also have symbiotic algae and undergo bleaching, making them suitable replacements for coral species in research.

The brown anemone, called Exaiptasia pallida, is used in the “CAREER: Exploring the Immunological Priming in a Basal Metazoan (Anthozoan)” programme. This species is found in the western Atlantic Ocean, sharing the same waters as Caribbean reefs. It is likely to encounter the same pathogens as corals in this area, making it susceptible to certain diseases that allow it to be used in place of corals in this research. By studying immunological priming in brown anemones, our understanding of the processes behind immunological defence in anthozoans, and the evolution of immunity in basal metazoans (species that diverged early on in evolution and have remained relatively unchanged since) will expand.

Immunological priming
Immunological priming is a process by which the immune response of an organism is strengthened by repeated exposure to a pathogen. This is common in more advanced species, such as humans and other vertebrates, but research suggests that priming could have developed much earlier in the evolutionary tree.

In his initial research proposal for the CAREER programme, Dr Rodriguez-Lanetty hypothesised that sub-lethal exposure to a pathogen could result in anthozoans establishing a defensive response that they will be able to express more effectively when they encounter the pathogen again in the future.

To determine if this is the case, brown anemones were repeatedly exposed to Vibrio coralliilyticus — a bacterial species known to cause morbidity and bleaching in both corals and anemones. It was found that three days of exposure to the bacterium could be considered “sub-lethal”, and anemones exposed to the pathogen twice were more likely to survive future encounters to it, than those naïve to it. This is an exciting finding that suggests learnt immune responses such as this are not limited to complex vertebrates. As a result, this has opened many doors for further research into the immunological processes of anthozoans.

Proposed model of Heat Shock Proteins (HSP), Capthesin and Glutamate Receptor (iGluR) roles in cnidarian molecular defense priming: (1) HSP are up regulated and some are extracellularly secreted where bind to peptides and act as DAMPs; (2) as DAMPs, HSP help with a faster activation of the innate complement system, and/or (3) interact and cause a quicker activation of outer host cell membrane TLRs; (4) intracellularly, up-regulated HSP proteins can be delivered into lysosomes in which they can also interact and activate endosomal cell membrane TLRs; (5) higher production of Capthesin are delivered into lysosomes in which they can also interact and activate endosomal cell membrane TLRs; (6) activated TLRs either from the outer membrane or endosomal membranes will trigger cell signaling pathways that will converge in the activation of transcription factors (likely NF-kappa β) that will ultimately induce the expression of immune-related genes (7) resulting in the production of potential pro-inflammatory molecules; (8) Higher expression of iGluR expressed on the outer membrane will also facilitate a faster sensing of potential DAMPs upon secondary exposure of pathogens. Adapted from a figure originally published in SCIENTIFIC REPORTS under the Creative Commons CC BY 4.0 license.

Differences in proteins between unexposed and exposed anemones were also identified, suggesting that this defensive mechanism is controlled at a molecular level. The identified proteins were similar to genes associated with immune responses in other organisms. One in particular was similar to ionotropic glutamate receptors (iGluR), which are associated with neurotransmissions in animals with a nervous system, and are common in exposed anemones. Again, using brown anemones as a model system, nine iGluR-like genes were identified and found to change when the animal was exposed to a pathogen. This is a particularly interesting finding, as it suggests these types of receptors are more widespread than previously thought, and that they originated as mechanisms for sensing cues early on in evolutionary history.

Research suggests that immunological priming could have developed much earlier in the evolutionary tree.

Based on these findings, future research will assess whether host responses to repeated infectious agent exposure are pathogen-specific, and how symbiotic microbes respond to immunological priming. These are exciting areas that with further improve our understanding of disease resistance in anthozoans.

Career development
Inspiring future generations is a vital part of the scientific process. An important component of the CAREER programme is outreach to students from high school to postgraduate levels, and particularly to minorities who are underrepresented in science. This is highly important as it encourages those that may not pursue careers in science to consider entering the field.

By 2050, 60% of the US’ population growth is expected to originate from the Hispanic community, however, Hispanic people are the least likely to enter higher education. For this reason, the educational aspect of the programme focuses on engaging Hispanic students and other minorities.

Conducting a summer science programme entitled “Aventura Cientifica”, Dr Rodriguez-Lanetty hopes to motivate minority high school students to consider scientific research as a career. This is inspired by his own experiences, attributing a large part of his success to the positive role models he encountered throughout school and extra-curricular activities.

Aventura Cientifica is a four-week long experience held at Florida International University that will involve high school students in subjects included in the CAREER programme, improving their confidence and appreciation for science. This is vital to ensure that people from all backgrounds have opportunities to advance their interests in science and ultimately pursue a career in research. It will also enable the future generation to continue protecting the environment, which will become increasingly more important over the coming years.