What Is a Host? Incorporating the Microbiota into the Damage-Response Framework

Abstract

Since proof of the germ theory of disease in the late 19th century, a major focus of the fields of microbiology and infectious diseases has been to seek differences between pathogenic and nonpathogenic microbes and the role that the host plays in microbial pathogenesis. Remarkably, despite the increasing recognition that host immunity plays a role in microbial pathogenesis, there has been little discussion about what constitutes a host. Historically, hosts have been viewed in the context of their fitness or immunological status and characterized by adjectives such as immune, immunocompetent, immunosuppressed, immunocompromised, or immunologically impaired. However, in recent years it has become apparent that the microbiota has profound effects on host homeostasis and susceptibility to microbial diseases in addition to its effects on host immunity. This raises the question of how to incorporate the microbiota into defining a host. This definitional problem is further complicated because neither host nor microbial properties are adequate to predict the outcome of host-microbe interaction because this outcome exhibits emergent properties. In this essay, we revisit the damage-response framework (DRF) of microbial pathogenesis and demonstrate how it can incorporate the rapidly accumulating information being generated by the microbiome revolution. We use the tenets of the DRF to put forth the following definition of a host: a host is an entity that houses an associated microbiome/microbiota and interacts with microbes such that the outcome results in damage, benefit, or indifference, thus resulting in the states of symbiosis, colonization, commensalism, latency, and disease.

Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework

“…However, these host-microbe interactions influence various aspects of host physiology, and when in homeostasis, the microbiota contributes significantly to maintaining host health. Importantly, the microbiota has profound effects on host immunity and susceptibility to microbial diseases and, therefore, alterations to the microbiota could lead to host-microbe interactions that can produce host damage (8). Both extrinsic and intrinsic factors can cause perturbations to the system, which could lead to alterations in host physiology with potential adverse effects on host health (159).…”

“…It is well recognized that medical devices, immunosuppressive therapies, and diseases such as AIDS have created patient populations highly susceptible to infections. This awareness ultimately led to the development of the concept of microbial opportunism and opportunistic pathogens, viewed as microbes with pathogenic potential that becomes manifest in the setting of a weakened host immune system (8,9).…”

“…The versatility of C. albicans in its pathogenic potential and the diversity of its disease entities, depending on infection site, position it in a unique situation: based on the various clinical manifestations as a function of host immune status, this pathogen may arguably fit within each of the classes outlined by the DRF (1,8). Accordingly, here we highlight some of the varied and site-specific diseases caused by this human pathogen ( Fig.…”

More wrinkles to Bt susceptibility

“…Overall, these results are in agreement with an emerging theme from a number of host-pathogen models; that the key in host survival following intestinal damage is the balancing of repair mechanisms (recovery) with defense mechanisms that eliminate microbial threats, including the indigenous microbiota. 8,9 A strength of this study is the comparison between the gut versus hemocoel response, which provide insight to which tissues and mechanisms to target for future studies and comparison to other systems. What remains to be determined from these studies is what host signaling pathways are involved across the breadth of larval responses to Bt and how the host host coordinates the local (gut) and systemic (hemocoel) response.…”

Friend, foe or food? Recognition and the role of antimicrobial peptides in gut immunity and Drosophila –microbe interactions

“…In this regard, the damage-response framework incorporates the associated microbiota into the definition of host and focuses on the interaction between microbes and hosts instead of microbial characteristics [112]. Consistent with this in Drosophila, the extent of damage to the host is the only variable that differentiates the types of host -microbe interactions [21].…”