Is a Microbe That Harms Only Immunocompromised Hosts Still a Pathogen?

Benjamin Acosta, Olivia Mathieson, Erin McKenney, Aram Mikaelyan, Autumn Sylvestri, Aurora Toennisson

(Author names listed alphabetically)

A microbe that causes no harm in most hosts, but induces damage in those with compromised immunity. The label pathogen seems to depend not on the microbe’s identity, but on the condition of the host.

This reveals an instability in how microbial roles are defined. Classical frameworks rely on outcome: pathogens cause disease. Yet outcomes of ecological interactions are contextual. Immune response, environmental stress, and developmental stage all shape what a microbe does. A taxon beneficial in one host may be lethal in another. This variability challenges the use of fixed terms like commensal, mutualist, or pathogen.

From one perspective, a pathogen is defined by its capacity to cause damage. But capacity is not expression. If damage only occurs when the immune system is impaired, is the microbe pathogenic, or merely present?

One response is to shift the focus from taxonomy to interaction. Casadevall and Pirofsky’s Host Damage-Response Framework proposes that disease results not from microbial presence alone, but from the host’s response to it. Damage may arise from immune overreaction as much as from microbial virulence. Under this model, the microbe’s status as pathogen is relational – it is a pathogen only when host conditions allow or provoke damage. 

Yet not all damage is pathogenic. A working definition of a pathogen must also include its capacity to extract resources from the host - whether through replication or nutrient theft. Without this functional link, any environmental trigger that induces host damage could be misread as pathogenic. Damage alone is insufficient; what matters is damage in the context of exploitation of resources. Pollen, for instance, does not evolve to provoke allergic responses, but may do so in sensitized hosts. Environmental triggers become biological damage not by design, but by interaction. The line between environment and pathogen blurs when the host becomes the site of interpretation.

Perhaps the question is not whether the microbe is a pathogen, but whether the language of microbial identity is adequate to describe context-dependent relationships. If roles shift with host condition, then categories that presume stability may obscure more than they clarify. It may be more accurate to describe what microbes do in given contexts, rather than what they are. In that framing, the same taxon might be harmless, helpful, or harmful depending on host immunity, ecological setting, and temporal dynamics.

The microbe is not the pathogen. The interaction is.

Note: This post was developed as a pedagogical exercise in collaborative synthesis and argument literacy, emerging from a discussion among three students and two faculty members in the M-lab Fun chat group, exploring how microbiomes challenge conventional views of inheritance and evolution.