Large diversity of serotypesRhinovirusesColdsStreptococcus Pneumonia, pneumoniae meningitis complement pathway in the extracellular environment, and complement products coat the bacteria, resulting in uptake of the organism by monocytes; by this means, the organism reaches its site of replication. Many bacteria (such as Shigella, enteroinvasive E. coli, M. tuberculosis, M. leprae, S. enterica serotype Typhi) use the inside of cells as a “hideout” that allows them to escape from antibodies and complement. Listeria monocytogenes can manipulate the cell cytoskeleton to spread directly from cell to cell, thus allowing the bacteria to evade immune defenses.
Resisting phagocytosis and bacterial killing in phagosomes. Phagocytosis and killing of bacteria by neutrophils and macrophages constitute a critical host defense against extracellular bacteria. The carbohydrate capsule on the surface of many bacteria that cause pneumonia or meningitis (S. pneumoniae, Neisseria meningitidis, H. influenzae) makes them more virulent by preventing phagocytosis of the organisms by neutrophils. Surface proteins that inhibit phagocytosis include proteins A (S. aureus) and M (S. pyogenes). Macrophages usually kill bacteria by fusion of the phagosome with the lysosome to form a phagolysosome. M. tuberculosis blocks fusion of the lysosome with the phagosome, allowing the bacteria to proliferate unchecked within the macrophage. Legionella produces a pore-forming protein called listeriolysin O and two phospholipases that degrade the phagosome membrane, allowing the bacteria to escape into the cytoplasm and avoid destruction in the macrophage. Legionella also secretes proteins that modulate small GTPases, master regulators of intracellular signaling to modify trafficking. Also, many bacteria make proteins that kill phagocytes, prevent their migration, or diminish their oxidative burst.
Escaping the inflammasome. The activation of the cytosolic inflammasome is one pathway of innate immune responses to microbes. It is stimulated by microbial products and culminates in the activation of caspases, which induce the secretion of the pro-inflammatory cytokines IL-1 and IL-18 and induce a form of cell death called pyroptosis (Chapter 5). Both inflammation and cell death limit microbial virulence and replication. Some bacteria, such as Yersinia and Salmonella, express virulence proteins that inhibit the formation of the mature inflammasome, suppress caspase activation, block signaling pathways that are required for inflammasome activation, or limit the access of other bacterial proteins to the inflammasome. All these mechanisms serve to disable various components of this host antimicrobial defense reaction.
Disruption of interferon pathways. Viruses have developed a large number of strategies to combat interferons (IFNs), which are mediators of early antiviral defense. Some viruses produce soluble homologues of IFN receptors that bind to and block the actions of secreted IFNs, or produce proteins that inhibit intracellular JAK/STAT signaling downstream of IFN receptors. RIG-I (RNA helicase retinoic acid inducible gene I protein) is a host cytoplasmic pattern recognition receptor for intracellular double-stranded RNA viruses. RIG-I inhibits signaling by this receptor, thus blocking the downstream IFN pathway and overcoming this host defense. Some viruses encode within their genomes homologs of cytokines, chemokines, or their receptors that act as competitive antagonists to inhibit immune responses. Finally, viruses have developed strategies to block apoptosis, which may give the viruses time to replicate, persist, or transform the infected host cell.