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Beginning at birth, microbial organisms enter and leave the human body, primarily through external and mucosal surfaces. Some of these predominantly commensal organisms become resident; others are transient; and still others establish latent foci in various tissue spaces. Over a lifetime, the host–pathogen interactions that take place in an average human determine colonization, microbiome composition, and susceptibility to infections as well as immune-related events such as vaccine responses, autoimmunity, and malignant transformation. The human host is a reservoir for hundreds of strains of viruses, thousands of bacterial species, and a scattering of fungi and parasites. When these organisms violate their niche, invade, or produce toxic products, and at the same time overcome innate and adaptive host defenses, virulent interactions take place and can lead to disease. Organisms have evolved a variety of strategies to overcome host defenses, evade the immune system, scavenge for nutrients, eradicate competing bacteria, and survive to spread to other hosts. At the macro level, infection in the lung is the culmination of a disruption in the epidemiologic triad comprising host, agent, and environment. At the molecular level, new mechanistic insights into the interactions between host susceptibility, pathogen virulence, and environmental risk factors continue to be discovered.

The immune system maintains surveillance for organisms that invade phagocytes, propagate, and resist killing, and also for organisms that invade nonphagocytic cells. Means by which microbes can be controlled range from physical clearance mechanisms, to phagocytosis (followed by oxidative or nonoxidative killing), to nutritional depletion (e.g., sequestration of iron, which is an essential nutrient for bacterial growth). The existence of heavy colonization or infection in the upper airways increases the potential for infection in the lungs by a variety of mechanisms, mostly by a simple dose effect, whereby a large burden of potentially pathogenic organisms overwhelms the clearance mechanism of the lungs. Although the alveolar spaces are generally sterile, low levels of microorganisms are continually inhaled into the lungs. Inoculation of the lungs can occur from a variety of sources, including aspirated oropharyngeal secretions, directly inhaled from ambient air (airborne) or as droplet nuclei, particularly in closed environments, where density is great and infected individuals can deposit organisms into the air. Although not common, organisms can also gain entry into the lung via hematogenous spread from the bloodstream to the lungs, perhaps most notably in Lemierre disease related to septic thrombophlebitis due to the Gram-negative anaerobe Fusobacterium necrophorum.

The quantity and species diversity of many of the organisms colonizing the upper airways can be stable over long periods, although transient colonization with a variety of microbes also occurs with some frequency, and these changes are often correlated seasonally and/or with concomitant infections with respiratory viruses. For example, Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are more frequently isolated from the nasopharynx or throat during the winter months.1–4

Whether these inhaled or aspirated microbes cause disease depends on the intersection ...

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