8/3/2019 Pa Tho Genesis of Streptococcus Pneumoniae
Infections
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Pathogenesis ofStreptococcus Pneumoniae Infections
NP carriage ofS. pneumoniae is required for transmission of
bacteria and for invasive disease.[80]
Pneumococci bind to mucosal epithelial cells of the
nasopharynx.[72]In normal healthy children,
NP carriage of pneumococci is transient and is not associated
with disease.[21]
However, disease
is caused by contiguous spread to the sinuses or middle ear,
aspiration into the lung, or invasionof the
bloodstream.[72]Progression to pneumonia requires additional
factors (e.g., antecedent
viral infections, lung injury, impaired host defenses, etc.).
Clearance of pneumococci is
facilitated by both humoral and cellular immune responses
involving monocyte/macrophages,polymorphonuclear leukocytes (PMNs),
anticapsular antibodies, and lymphocytes.[72]Further,
nonimmune factors (e.g., anatomical barriers, cilia, mucins,
colectins, surfactant, etc.) are also
critical to clear bacteria.[81]
Prognosis of pneumococcal infections depends upon both host-
andorganism-dependent factors.[72]
The polysaccharide capsule serves as a major pathogenic factor
for invasive disease by
preventing phagocytosis.[72]
Humoral antibodies directed against the polysaccharide
capsule
usually develop within the first 2 years of life; colonization
with specific serotypes may elicitserotype-specific humoral
antibodies.
[72,82]Protection is serotype specific but some cross-
serotype protection is found in some cases.[80]
However, these anticapsular antibodies (whetheracquired
naturally or by vaccination) provide incomplete protection against
IPD.[80,83,84]
Antibodies to serotype 19F reduced colonization rates in
some[80]
but not all studies.[82]
Additional serotype-independent factors are important in
preventing or resolving pneumococcaldisease and
carriage.[80]Components of the pneumococcal cell walls recruit PMNs
to the lung,
enhance permeability of alveolar epithelial cells, and stimulate
cytokine release.[72]The host'sprimary cellular immune response
against S. pneumoniae is mediated by alveolar macrophages
(AMs); neutrophils represent a second line of defense.[85]
The immune response against S.
pneumoniae is complex, involving proinflammatory cytokines
released by AMs [e.g., tumor
necrosis factor- (TNF-) and interleukin-1 (IL-1)],
[81,86]
macrophage inflammatory protein-2(MIP-2),[81]
upregulation of myriad cytokines and chemokines (e.g., IL-6,
IL-8, and IL-18)[81,87]
],
and adhesion molecules on endothelial cells.[81]
Toll-like receptors (TLRs), expressed on bothimmune and
nonimmune cells, are important to recognize S. pneumoniae and
promote
bactericidal response by mononuclear cells.[88]
Further, granulocyte-colony stimulating factor
(G-CSF) recruits and stimulates PMNs, facilitating phagocytosis
and oxidative burst.[81]
Tlymphocyte cells also play a role in eradicating pathogens from
the alveolar spaces .[81]Dendritic
cells present the antigen to T cells, expanding CD4+ T cell
responses, specifically T-helper 1
(Th1) and Th2 phenotypes.[81]
Th1 immunity, characterized by production of IL-2, IL-12,
IL-18,granulocyte monocyte-colony stimulating factor (GM-CSF), and
interferon- (INF-), is critical
to the eradication of pneumococci.[81]Interestingly, deficiency
of IL-12 in humans has been
associated with recurrent pneumococcal pneumonia.
[89]
Th2 cells release cytokines that stimulateB cell antibody
production, thereby facilitating humoral responses.[81]
Other cells/productscritical to eradicating pneumococci include
antibody- and complement-mediated opsonization;
IL-1 receptor-associated kinase-4- and nuclear factor
kappaB[90]; and memory T cells (generated
in the spleen).[91]
In summary, eradication of pneumococci is achieved by myriad
interactions
involving anatomical boundaries, diverse cells (immune and
nonimmune), cytokines,chemokines, and humoral antibodies, and other
factors that work in concert. Deficiency of
specific immune components (e.g., asplenia,
hypogammaglobulinemia, B cell dysfunction, etc.)
