Pneumonia pathogens through mucociliary clearance. Mucin also acts

Pneumonia is a lower respiratory tract
infection, causing inflammation and consolidation of the lung parenchyma and impairing
its gas exchange function. Infection is primarily caused by bacterial or viral
pathogens, and less commonly by fungal and parasitic organisms (1). Most cases of community acquired
pneumonia (CAP) are bacterial in nature (2), with Streptococcus pneumoniae (pneumococcus) being the most common
causative agent, accounting for 20-60% of all CAP cases (3).


A number of factors can increase the
susceptibility of bacterial lung infections, such as age (> 65 years
old), smoking, and chronic obstructive pulmonary disorder (COPD) (4). In this case, the patient presents
with the major risk factors associated with lung infection, which increases the
likelihood of respiratory disease.

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Spread and


S. pneumoniae is a gram-positive, -hemolytic pathogen; it is an
opportunistic invader and colonizer of the upper respiratory tract, and is most
commonly found in the nasopharynx (5). It exists asymptomatically in a
healthy carrier, but becomes pathogenic when shown to be infiltrating the lower
respiratory tract (6). Therefore, colonization is a
prerequisite for pneumococcal disease (7), as it drives the virulence factors necessary
for the development of pneumonia.


S. pneumoniae is spread through person-to-person
contact via respiratory droplets, either from an asymptomatic carrier or
symptomatic individual. Local spread within the nasopharynx can extend into
normally sterile sites, including the sinuses and lungs. Aspiration of bacteria from the
nasopharynx into the lower respiratory tract is the most common route of
acquisition of the pathogen into the lungs, accounting for 90% of pneumonias (3).


Immune Response
to S. pneumoniae and Pathogenesis


In the nasopharynx, pneumococcus encounters mucus,
which acts as the first-line defense and serves as a physical barrier against
invading pathogens through mucociliary clearance. Mucin also acts as a scaffold
for antimicrobial proteins, thus the polysaccharide capsule encasing
pneumococci have evolved to limit opsonisation by complement and antibody (8). Additionally, pneumococcal capsules
are negatively charged, which enforces repulsion of the bacterium from the
anionic mucous barrier, facilitating the avoidance of destruction through
mucociliary clearance (8).


Once colonizing bacteria has reached the epithelial
surface, lipopoteichoic acids of pneumococci are recognized by Toll-like
receptor 2 (TLR2). Neutrophils are initially recruited to the site of infection,
but its response to pneumococcal acquisition is insufficient in the absence of
adaptive immunity. In the lower respiratory tract, the pulmonary capillary bed
contains a vast reservoir of intravascular neutrophils, which can be rapidly
activated to the alveolar space during infection. Activation of pattern
recognition receptors (PRRs) also promotes inflammatory response by cytokines, which
activates and enhances macrophage clearance of the invading pathogen in the
alveoli (9).


Alveolar macrophage offers first-line protection in
pulmonary host defense, by killing pathogens through generation of reactive
oxygen species (ROS) and serine proteases. However, they exhibit less
phagocytic activity and oxidative burst than other macrophages, and are less
likely to activate T-cells (10). Altogether, this leads to increased likelihood
of pathogen evasion from the immune system. In the presence of low numbers of S. penumoniae in the lungs, alveolar
macrophages are able to identify (through PRR), phagocytose and kill the
invading bacteria (10). However, high levels of infection in
the lung can overwhelm the alveolar-mediated clearance. This initiates an
inflammatory-response propagated by pro-inflammatory cytokines (such as TNF, IL6, and IL8), and recruitment of
additional mechanisms of clearance (such as neutrophils) to the air spaces (11). Activation of the complement system by
C-reactive protein also aids in leukocyte recruitment, amplifying immune
clearance within the alveolar spaces during acute-phase infection (12).


In the resolution of inflammation, alveolar
macrophages remove apoptotic neutrophils, however, failure to clear these cells
may lead to further tissue injury by the release of ROS and proteases, causing
chronic inflammation (13).


It is the massive inflammatory response in the lung
parenchyma, caused by the invading pathogen (S. pneumoniae), that
constitutes as pneumonia. It is marked by neutrophils and inflammatory exudates
filling alveolar spaces, impairing lung function and resulting in the clinical
hallmarks of the disease, such as shortness of breath, consolidation in the
lungs and chest pain.


Relation to the


In regard to the patient, his COPD and old age put him at greater risk of pneumonia. This can be
attributed to impaired pulmonary function caused by emphysema and chronic bronchitis
in COPD, and a general weakened immune system due to old age. Additionally, the
use of inhaled corticosteroids in the treatment of COPD may have increased the
risk of pneumonia (14). Although the specific mechanisms of
this is not clearly known, the anti-inflammatory properties and local immune
suppression of the airways may be contributing factors to this effect (2).


Smoking produces structural changes in the respiratory
tract, such as disruption of the ciliated respiratory epithelium, impairing its
ability to clear invasive agents. Reduction in ciliary motility means that
removal of pathogenic substances can invade the lower respiratory tract,
resulting in overwhelming infection. Furthermore, tobacco smoke may promote the
production of pro-inflammatory mediators by epithelial cells, hence worsening
the pneumococcus infection (15). Smoking also increases the likelihood
of development of lung cancer, coronary heart disease, and stroke. Since the
patient is a current smoker, smoking cessation is recommended to prevent
further exacerbation of COPD, recurrence of pneumonia, and the development of
other diseases related to smoking.