The amphibian complement system and chytridiomycosis

Abstract

Understanding host immune function and ecoimmunology is increasingly important at a time when emerging infectious diseases (EIDs) threaten wildlife. One EID that has emerged and spread widely in recent years is chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), which is implicated unprecedented amphibian declines around the world. The impacts of Bd have been severe for many amphibian species, but some populations have exhibited signs of persistence, and even recovery, in some regions. Many mechanisms may underpin this pattern and amphibian immune responses are likely one key component. Although we have made great strides in understanding amphibian immunity, the complement system remains poorly understood. The complement system is a nonspecific, innate immune defense that is known to enhance other immune responses. Complement activation can occur by three different biochemical pathways and result in protective mechanisms, such as inflammation, opsonization, and pathogen lysis, thereby providing protection to the host. We currently lack an understanding of complement pathway activation for chytridiomycosis, but several studies have suggested that it may be a key part of an early and robust immune response that confers host resistance. Here, we review the available research on the complement system in general as well as amphibian complement responses to Bd infection. Additionally, we propose future research directions that will increase our understanding of the amphibian complement system and other immune responses to Bd. Finally, we suggest how a deeper understanding of amphibian immunity could enhance the conservation and management of amphibian species that are threatened by chytridiomycosis.

Leveraging Multi‐Level Biomarkers Using Machine Learning: Identifying Physiological and Skin Microbial Dynamics in Bd ‐Resistant Amphibians

“…The identification of CORT and BKA as the main predictors of infection status aligns with their previously established functions in amphibian physiology and immunity, further supporting their biological relevance in Bd –host interactions (Peterson et al. 2013; Rodriguez and Voyles 2020). The integration of microbiome data into predictive models could widen the range of ML applications for a holistic understanding of the interactions among host physiology, microbial ecology, and pathogen dynamics (Hernández Medina et al.…”

“…BKA is a good predictor of innate immunity that shows a complement response in ecological immunology (Demas et al. 2011) and is also a useful biomarker in studies of Bd infection (Rodriguez and Voyles 2020). In our study, Bd‐ infected juvenile frogs had significantly lower BKA.…”

Leveraging Multi‐Level Biomarkers Using Machine Learning: Identifying Physiological and Skin Microbial Dynamics in Bd ‐Resistant Amphibians

“…The identification of CORT and BKA as the main predictors of infection status aligns with their previously established functions in amphibian physiology and immunity, further supporting their biological relevance in Bd –host interactions (Peterson et al. 2013; Rodriguez and Voyles 2020). The integration of microbiome data into predictive models could widen the range of ML applications for a holistic understanding of the interactions among host physiology, microbial ecology, and pathogen dynamics (Hernández Medina et al.…”

“…BKA is a good predictor of innate immunity that shows a complement response in ecological immunology (Demas et al. 2011) and is also a useful biomarker in studies of Bd infection (Rodriguez and Voyles 2020). In our study, Bd‐ infected juvenile frogs had significantly lower BKA.…”

Bacterial killing assays in ecoimmunology require cross-validation by agreement statistics

“…However, natural antibody and complement proteins have the potential capacity to impact the properties of light attenuation, and through their very actions (zymogen cleavage, aggregation, agglutination of microbes, etc.) could change the shape, size, and density of particles in suspension ( Schmid, 2001 ; Rodriguez and Voyles, 2020 ; Parham, 2021 ).…”

“…We suggest several experimental tests of changes in optical properties of immune components, which will help to elucidate mechanistic modes of killing beyond simple BKA values across species and antigenic stimulants (e.g. Millet et al, 2007 ; Rodriguez and Voyles, 2020 ). For example, heat-killed bacteria or common antigens (e.g.…”

Chromosome‐level genome of the green odorous frog ( Odorrana margaretae ) provides insights into the evolution of transposable elements and olfaction‐related gene families in frogs

“…2A), with many expansions enhancing innate immunological functions. The complement cascade is a crucial biochemical immune process for amphibians (Rodriguez & Voyles, 2020). Complement‐related functions in green odorous frogs, including lectins, complement, and coagulation cascades, and complement activation, indicate potent innate immunity against pathogens (Janeway et al, 2001).…”

Leveraging Multi‐Level Biomarkers Using Machine Learning: Identifying Physiological and Skin Microbial Dynamics in Bd ‐Resistant Amphibians

“…The identification of CORT and BKA as the main predictors of infection status aligns with their previously established functions in amphibian physiology and immunity, further supporting their biological relevance in Bd –host interactions (Peterson et al. 2013; Rodriguez and Voyles 2020). The integration of microbiome data into predictive models could widen the range of ML applications for a holistic understanding of the interactions among host physiology, microbial ecology, and pathogen dynamics (Hernández Medina et al.…”

“…BKA is a good predictor of innate immunity that shows a complement response in ecological immunology (Demas et al. 2011) and is also a useful biomarker in studies of Bd infection (Rodriguez and Voyles 2020). In our study, Bd‐ infected juvenile frogs had significantly lower BKA.…”

Bacterial killing assays in ecoimmunology require cross-validation by agreement statistics

“…However, natural antibody and complement proteins have the potential capacity to impact the properties of light attenuation, and through their very actions (zymogen cleavage, aggregation, agglutination of microbes, etc.) could change the shape, size, and density of particles in suspension ( Schmid, 2001 ; Rodriguez and Voyles, 2020 ; Parham, 2021 ).…”

“…We suggest several experimental tests of changes in optical properties of immune components, which will help to elucidate mechanistic modes of killing beyond simple BKA values across species and antigenic stimulants (e.g. Millet et al, 2007 ; Rodriguez and Voyles, 2020 ). For example, heat-killed bacteria or common antigens (e.g.…”

Chromosome‐level genome of the green odorous frog ( Odorrana margaretae ) provides insights into the evolution of transposable elements and olfaction‐related gene families in frogs

“…2A), with many expansions enhancing innate immunological functions. The complement cascade is a crucial biochemical immune process for amphibians (Rodriguez & Voyles, 2020). Complement‐related functions in green odorous frogs, including lectins, complement, and coagulation cascades, and complement activation, indicate potent innate immunity against pathogens (Janeway et al, 2001).…”

Leveraging Multi‐Level Biomarkers Using Machine Learning: Identifying Physiological and Skin Microbial Dynamics in Bd ‐Resistant Amphibians

“…The identification of CORT and BKA as the main predictors of infection status aligns with their previously established functions in amphibian physiology and immunity, further supporting their biological relevance in Bd –host interactions (Peterson et al. 2013; Rodriguez and Voyles 2020). The integration of microbiome data into predictive models could widen the range of ML applications for a holistic understanding of the interactions among host physiology, microbial ecology, and pathogen dynamics (Hernández Medina et al.…”

“…BKA is a good predictor of innate immunity that shows a complement response in ecological immunology (Demas et al. 2011) and is also a useful biomarker in studies of Bd infection (Rodriguez and Voyles 2020). In our study, Bd‐ infected juvenile frogs had significantly lower BKA.…”

Bacterial killing assays in ecoimmunology require cross-validation by agreement statistics

“…However, natural antibody and complement proteins have the potential capacity to impact the properties of light attenuation, and through their very actions (zymogen cleavage, aggregation, agglutination of microbes, etc.) could change the shape, size, and density of particles in suspension ( Schmid, 2001 ; Rodriguez and Voyles, 2020 ; Parham, 2021 ).…”

“…We suggest several experimental tests of changes in optical properties of immune components, which will help to elucidate mechanistic modes of killing beyond simple BKA values across species and antigenic stimulants (e.g. Millet et al, 2007 ; Rodriguez and Voyles, 2020 ). For example, heat-killed bacteria or common antigens (e.g.…”

Chromosome‐level genome of the green odorous frog ( Odorrana margaretae ) provides insights into the evolution of transposable elements and olfaction‐related gene families in frogs

“…2A), with many expansions enhancing innate immunological functions. The complement cascade is a crucial biochemical immune process for amphibians (Rodriguez & Voyles, 2020). Complement‐related functions in green odorous frogs, including lectins, complement, and coagulation cascades, and complement activation, indicate potent innate immunity against pathogens (Janeway et al, 2001).…”