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Host Defenses to Extracellular Bacteria

Marcos C. Schechter, Sarah W. Satola, David S. Stephens

The human host has developed protective mechanisms to interact Conversely, bacteria typically classified as “intracellular” can have
with the multitude of bacterial species encountered in nature. an extracellular component to their lifecycle (e.g., Mycobacterium
These host defenses include nonspecific mechanisms of clearance, tuberculosis in cavitary lesions).
as well as innate and specific adaptive immune responses. Partly Host defense mechanisms against extracellular bacteria are
because of these mechanisms, the vast majority of bacterial species a continuum. The innate and adaptive immune systems cooperate
do not cause human disease. Many bacterial species have estab- to protect the host from extracellular bacterial infections. The
lished symbiotic or commensal relationships with the human innate immune system senses bacteria through pattern recognition
host and colonize skin and mucosal surfaces. These commensals receptors (PRRs; Chapter 3). These receptors activate antimicrobial
are generally of low virulence except in individuals whose host defenses and stimulate the adaptive response, all while balancing
defenses are compromised. Given the diversity of the microbial excessive immune and inflammatory responses with the need
world, a relatively few pathogenic bacterial species or subpopula- to protect against the infecting pathogen. 2
tions of those species have evolved virulence factors or strategies
that can overcome or circumvent intact human host defense CLINICAL PEARLS
mechanisms to cause localized or systemic disease. Distinguishing Clinical Characteristics of
Important bacterial pathogens of clinical importance reside Infections With Extracellular Bacteria
mostly extracellularly (Table 27.1). Examples are bacterial
pathogens typically labeled extracellular, such as Streptococcus • Sterilizing immunity
pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, • Colonization of mucosal surfaces often precedes disease
Neisseria meningitidis, Neisseria gonorrhoeae, and Bordetella • Causes of pyogenic infections
pertussis, which are transmitted from one individual to another • T-helper (Th)17 response critical in generating a neutrophilic response
by close contact. Other “extracellular” bacterial pathogens, such • Antibodies are protective for some of the major pathogens
• Effective vaccines available for many of the major pathogens
as Clostridium spp. Vibrio cholerae, Shigella dysenteriae, entero-
pathogenic Escherichia coli, and Bacillus anthracis, are transmitted
through food, water, animal, or other environmental contact. CLEARANCE AND NONSPECIFIC HOST DEFENSES
Staphylococcus aureus is an important extracellular pathogen for AT MUCOSAL EPITHELIAL SURFACES
humans and can be acquired from other humans, from animals,
or through environmental contact. Acquisition of these pathogenic Bacteria first encounter a physical barrier, which comprises skin,
bacteria may be transient, result in variable intervals of coloniza- mucus and mucosal surfaces, and the normal microbiota, as well
tion, or rapidly cause localized or systemic disease. as nonspecific factors, such as nutrient limitation (e.g., iron),
Extracellular bacterial pathogens can produce acute inflam- and antimicrobial proteins or peptides. Intact skin and mucosal
matory and purulent infectious diseases, such as meningitis, surfaces provide complex chemical and biological obstacles to
septicemia, pneumonia, urethritis, pharyngitis, inflammatory extracellular bacteria and are an important line of defense prevent-
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diarrhea, cellulitis, and abscesses and/or produce disease by the ing the invasion of these pathogens and their products. Humans
release of toxins. Disease associated with some extracellular commonly carry extracellular pathogens asymptomatically on
bacteria (e.g., Helicobacter pylori) results from chronic coloniza- skin and at respiratory and gastrointestinal (GI) mucosal surfaces.
tion. Susceptibility to extracellular bacterial pathogens is enhanced To cause disease, pathogens breach or disrupt epithelial barriers.
by hereditary, acquired, or age-related defects in innate or adaptive Damage to epithelial barriers as a result of trauma; coinfections;
host defenses. Resistance to extracellular bacterial pathogens or drugs, such as those used in chemotherapy; environmental factors,
their toxins can be accentuated by chemoprophylaxis, by vaccines, such as smoking, allergies, or low humidity; and catheterization
and by other immune modulation processes (e.g., passive immune and intubation circumvent these barriers and allow bacteria
globulin administration). Caution is urged in the interpretation access to subcutaneous tissues, blood vessels, and other normally
of the term “extracellular.” The classification of bacteria as sterile sites. Additionally, acquired and genetic diseases affecting
“extracellular” and “intracellular” is primarily based on observa- epithelial barriers are also linked to increase in infections.
tions in vitro and has been challenged by some authors, as some The human epithelium has evolved to prevent colonization and
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”extracellular” bacterial species invade host cells as a part of invasion by pathogenic organisms. Skin is a relatively dry, acidic
their normal lifecycle and during steps in the disease process (pH 5–6) barrier that contains growth-inhibiting fatty acids and
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(e.g., S. aureus, S. pneumoniae, S. pyogenes, N. meningitidis). antimicrobial peptides (AMPs) (see below), characteristics that
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