To Care Or To Kill: When The Needs Of The Many Outweigh The Needs Of The Few.

Project Information

CareKill

Grant agreement ID: 101063449

DOI

10.3030/101063449

Project closed

EC signature date 4 August 2022

Start date 1 October 2022

End date 30 September 2024

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 214 934,40

Coordinated by

KOBENHAVNS UNIVERSITET
Denmark

Periodic Reporting for period 1 - CareKill (To Care Or To Kill: When The Needs Of The Many Outweigh The Needs Of The Few.)

Reporting period: 2022-10-01 to 2024-09-30

Summary of the context and overall objectives of the project

Social living among animals, while advantageous for survival and cooperation, inherently increases the risk of disease transmission, as evidenced by pandemics like SARS-CoV-2. This challenge is acute in social insects such as termites, which live in densely populated colonies with low genetic diversity, often in pathogen-rich environments like soil and decaying wood. Despite these vulnerabilities, termites demonstrate remarkable resilience to disease, employing sophisticated "social immunity" strategies to mitigate outbreaks within their colonies. These strategies include behavioral adaptations such as grooming and isolation of infected individuals, as well as chemical and immune responses. A key component of this immunity is the behavioral dichotomy to either care or kill infected nestmates, balancing the preservation of worker resources against the prevention of pathogen spread. However, the factors driving this decision—such as pathogen dose, infection progression, and genetic influences—remain poorly understood. Moreover, the potential role of immune and behavioral memory in shaping these decisions is largely unexplored.
Overall Objectives
1. Behavioral Dynamics: How infection dose and progression influence the care-kill switch in social termites.
2. Genetic and Molecular Mechanisms: What genes and pathways govern the assessment of risk and the resulting care or kill behavior.
3. Memory and Adaptation: How previous encounters with pathogens influence subsequent care-kill decisions, exploring the existence of social immune memory.
Through behavioral experiments, advanced genomic analyses, and collaboration with global experts, CareKill will generate a comprehensive model of termite social immunity. By integrating findings from ecology, molecular biology, and behavior, the project will offer fundamental insights into adaptive disease management strategies in social animals.

Pathway to Impact
Scientific Advancements: Establishing a robust framework for understanding social immunity, which has implications for ecological immunology, behavioral ecology, and public health analogies. CareKill will also fill gaps in the understanding of termite resilience in high-pathogen environments.
Conservation and Management: Providing knowledge that can inform the preservation of termite species, essential for soil health and ecological balance.
Broader Applications: Insights into adaptive collective immunity could inspire innovative approaches in human disease management and bio-inspired technologies. This work aligns with global priorities in biodiversity, ecosystem health, and sustainable living. Its findings may have strategic relevance for addressing the challenges of disease spread in social systems, both natural and human-made.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Overview of Activities and Progress:
The "CareKill" project aimed to investigate the behavioral and genetic mechanisms behind termite responses to pathogens, specifically the transition from caretaking to killing behaviors. The research was divided into three work packages (WP):
1. WP1: Behavioral Switch from Care to Kill
o Progress: The initial hypothesis that termites would switch from caretaking to killing in response to Metarhizium spp. infection was not supported. Experiments showed no significant behavioral responses in fungus-farming termites (Macrotermes bellicosus) to different doses of Metarhizium fungi.
o Achievement: The project adapted by isolating ecologically relevant fungal pathogens from the termite environment, leading to a revised experimental approach. Preliminary analysis of these new pathogens indicated that termites exhibited caretaking behaviors (grooming and antennation) but no killing behaviors (such as leg clipping or cannibalism).
o Key Outcome: The research revealed that the response to pathogens in termites may vary significantly by species and pathogen type, prompting a reevaluation of social immunity research and potentially transforming our understanding of termite disease ecology.
2. WP2: Genetic Factors in Risk Assessment
o Progress: RNA samples were collected from termites involved in infection experiments for gene expression analysis. However, the analysis is still ongoing, with no definitive milestones achieved yet due to the unexpected results from WP1.
o Achievement: RNA isolation and sequencing for differential gene expression were successfully completed, and data is under analysis with a bioinformatics collaborator. The planned experiments for understanding gene regulation in response to pathogens are still in progress.
o Key Outcome: This work is expected to provide insight into the genetic pathways involved in termite risk assessment, though results are pending.
3. WP3: Role of Experience and Immunological Memory
o Progress: This work package was not initiated due to the unforeseen ecological differences between the focal termite species and previously studied species. The team decided to focus on identifying relevant pathogens, which forms a foundation for future investigations into social immunity and memory.
o Achievement: No progress in this work package, as the planned experiments could not proceed due to the need to adapt the research focus.
Training and Knowledge Transfer:
• Scientific Training: The fellow received training in RNAseq techniques, field collection, microbiology, and immunology, successfully applying these skills in the research.
• Knowledge Transfer: The fellow contributed to the growth of social immunity research within the host lab, trained students, and helped expand international collaborations, including with universities in Brazil and Germany.
Revised Research Approach:
• The unexpected results from WP1 prompted a shift in focus. New work packages (A and B) were developed to identify the fungal pathogens relevant to the termites' environment and assess their impact on termite social immunity.
• The project also contributed to isolating novel fungal species that may serve as new pathogens in future studies of social immunity.
Impact and Contribution:
• The project's findings open new avenues for understanding the ecological dynamics of social immunity in termites, with potential implications for broader research in social animals' disease management.
• The research has laid the groundwork for continued studies into the diverse pathogen pressures termites face in the wild and how they manage these threats through social immune behaviors.
• The fellowship has helped expand the fellow’s technical skills, collaborative network, and research leadership, while also contributing significantly to the field of ecological
Future Directions:
• The project is now positioned to contribute valuable insights into the role of pathogen diversity in shaping social immunity strategies in termites, setting the stage for future work on immunological memory and pathogen recognition.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Key Results:
1. Behavioral Findings:
The project aimed to determine the behavioral switch from caretaking to killing in termite colonies when exposed to pathogens. Contrary to expectations, the fungus-farming termite species, Macrotermes bellicosus, did not exhibit the anticipated killing behaviors (such as leg clipping or cannibalism) in response to Metarhizium anisopliae. Instead, caretaking behaviors (such as grooming and antennation) were observed, but only in response to a range of newly isolated ecologically relevant fungal pathogens. These findings suggest that termite responses to pathogens can vary dramatically depending on the species and the specific pathogen, highlighting the need for a more tailored approach to social immunity research in termites and other social insects.
2. Gene Expression and Risk Assessment:
The project also sought to identify the genetic mechanisms underlying the termite response to pathogen threats. RNA was successfully extracted from termite samples, and sequencing has been performed, though results are still under analysis. This research will eventually provide insight into the immune pathways involved in risk assessment and the decision to care for or kill an infected nestmate.
3. Pathogen Diversity and Social Immunity:
One of the key results of the project is the identification of a diverse range of fungal pathogens within the termite environment. This opens up new opportunities for future research into the ecological pressures termites face, which are poorly understood compared to other social insects. The unexpected findings have emphasized the importance of pathogen-specific research, shifting the focus of the study from a general pathogen model (e.g. Metarhizium) to a more ecological-based approach, considering the variety of pathogens termites encounter in their environment.
4. International Collaboration:
The project led to international collaborations, particularly with researchers in Africa, Brazil, and Germany. Expanding these collaborations could enhance the scope of the research and facilitate the exchange of knowledge and resources, especially in the context of global biodiversity and conservation efforts.