Using the immune system to understand vertebrate-microbiome interactions and evolution

An animal’s “microbiome” consists of all the microorganisms that live on and inside it. The microbiome interacts with the animal’s immune system in complex ways. How an animal has both a highly effective immune system, but also a highly diverse microbiome that potentially contains pathogens, is achieved through adaptive immunity that has variable responses to detected threats.

One job of the immune system is to monitor the microbes in an animal’s gut and to stop potential pathogens from crossing over into the blood by tagging them with immunoglobulin A (IgA). This proposal will optimize a procedure developed in humans, called “IgA-Seq”, for application to birds. IgA-Seq sorts a microbiome into two populations, based on whether or not each individual microbe has been tagged with IgA (by the host).

The separate populations can then be sequenced and analyzed, to determine who the host sees as a potential threat and what genes those potential threats have. Completing this research will provide a view of the microbiome from the lens of the host’s immune system. This research has implications for multiple fields of study and, once optimized, will be a non-lethal and novel link between the immune system and the microbiome, for use in wild animal studies.

To promote future research, the researchers will create video tutorials of the entire process. To promote future generations of research, the researchers will facilitate observations of the field work and handling of wild birds by local elementary aged children.

The gastrointestinal epithelium is especially vulnerable to microbial infection, because vertebrates bring microbes into their digestive tract on food and the process of digestion occurs in a protected and nourishing environment. Vertebrates have gut-associated lymphoid tissue and immunological mechanisms that monitor and manage the gut microbiome, such as coating a potential pathogen with Immunoglobulin A.

Whether a microbe is tagged with IgA is not random and minimizes specific threats to the host without causing a systemic immune response or inflammation, which can be costly to produce. Therefore, we can use IgA to better understand the ecology and evolution of the vertebrate microbiome because it signifies how the host views and curates its microbiome to maximize host fitness.

The primary hypothesis of this proposal is that the interaction between the host’s immune system (via IgA) and the commensal gut microbiome is a central regulator of host-microbiome dynamics and key to understanding the evolution of the microbiome as a trait of the host. To address this hypothesis, we propose one initial research aim: optimize the method IgA-Seq, developed in humans, that sorts a microbiome cell-by-cell into populations based on whether an IgA is attached.

Using unsorted, IgA positive (IgA+) and IgA negative (IgA-) cell populations will identify the “core” microbiome and quantify persistence of microbial taxa and functions within and across individuals and species.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.