Figure 1. Overview of immune response mechanisms during MRSA infection.
The body has three lines of defense against MRSA infections. (A) Mucosal
immune response. The mucosal surface is in direct contact with
pathogens. The key strategy of the mucosal immune response is to
generate antigen-specific IgA antibodies in the external secretions.
This process occurs at Peyer’s patches (PP), and its key function is the
sampling of antigens. To facilitate this sampling, microfold (M) cells,
specialized phagocytic cells in the PP, can directly swallow and
transport antigens in the nasal or intestinal cavity to DCs via
phagocytosis. In the PP, through antigen presentation, IgA-committed
B-cell (IgA+ B cells) are induced to develop and finally produce dimeric
(or polymeric) forms of IgA after proliferation and differentiation at
effector sites. Ultimately, these forms of IgA become secretory IgA by
binding to polymeric Ig receptors (SCs). SIgAs are then released into
the nasal passage and intestinal tract, binding and “coating”
offending pathogens, thus blocking pathogen invasion. (B) Innate immune
response. The complement system is activated through the classical
pathway, lectin pathway and alternative pathway. Some complement
fragments, such as C3b formed by C3 convertases cleaving the C3 protein,
can exert phagocytosis through binding with the complement receptor
(CR). The membrane attack complex (MAC) is formed and directly leads to
cell lysis. Moreover, other complement fragments, such as C3a and C5a,
can trigger a series of chemotactic and proinflammatory responses to
facilitate neutrophil migration to the site of infection. Neutrophils
recruit and migrate to infection sites along a concentration gradient of
chemokines secreted or released by activated host cells or complement
components such as C5a. Finally, neutrophils are primed, activated and
stimulate bacterial clearance by phagocytosis and bactericide.
Gradually, the invading bacteria are killed, and any remaining
neutrophils die off via apoptosis and are cleared by macrophages. (C)
Adaptive immune response. As pathogens are degraded, antigenic peptides
can be presented by dedicated antigen-presenting cells, such as DCs and
Mφs, to T-lymphocytes, further activating the host adaptive immune
response. When stimulated directly or indirectly, B cells differentiate
and produce antibodies, which specifically bind with bacteria to
eliminate pathogens. When bacteria enter the cells, antigen-specific T
cells are stimulated and differentiate into CD8+ T cells. These cells
recognize and specifically bind to infected cells (targeted cells)
invaded by antigens, activate lysosomal enzymes in targeted cells, and
finally lead to the lysis and death of targeted cells. The antigens in
the cells lose are bound and immobilized by the antibodies and are then
phagocytosed. Ultimately, MRSA infection is inhibited.
Table 1. MRSA virulence factors that contribute to immune evasion and
their functions in host immune responses