**microbe detection paradox **

The innate immune system's detection of pathogens can be paradoxical due to the positioning of toll-like receptors facing the lysosome lumen, where successful pathogens would not present their nucleic acids. The immune system may overlook successful pathogens inside host cells, as their nucleic acids are not readily exposed for detection. Despite this paradox, knocking out toll-like receptors can worsen infections, indicating their role in recognizing pathogen nucleic acids. Not all pathogens within an inoculum execute virulence plans successfully, as evidenced by the Legionella study showing only 80% success in bacterial phagosome formation. Similarly, in viral infections, the particle-to-PfU ratio reveals that not all virions are ultimately infectious. Thus, the immune system may be poised to detect errors or unsuccessful pathogen replication rather than actively pinpointing successful intracellular pathogens.