Abstract
Phagocytosis of bacteria by innate immune cells is a primary method of bacterial clearance during infection. However, the mechanisms by which the host cell recognizes bacteria and consequentially initiates phagocytosis are largely unclear. Previous studies of the bacterium Pseudomonas aeruginosa have indicated that bacterial flagella and flagellar motility play an important role in colonization of the host and, importantly, that loss of flagellar motility enables phagocytic evasion. Here we use molecular, cellular, and genetic methods to provide the first formal evidence that phagocytic cells recognize bacterial motility rather than flagella and initiate phagocytosis in response to this motility. We demonstrate that deletion of genes coding for the flagellar stator complex, which results in non-swimming bacteria that retain an initial flagellar structure, confers resistance to phagocytic binding and ingestion in several species of the gamma proteobacterial group of Gram-negative bacteria, indicative of a shared strategy for phagocytic evasion. Furthermore, we show for the first time that susceptibility to phagocytosis in swimming bacteria is proportional to mot gene function and, consequently, flagellar rotation since complementary genetically- and biochemically-modulated incremental decreases in flagellar motility result in corresponding and proportional phagocytic evasion. These findings identify that phagocytic cells respond to flagellar movement, which represents a novel mechanism for non-opsonized phagocytic recognition of pathogenic bacteria.
Highlights
Pathogen recognition by the innate immune system is one of the first lines of defense in cellular immunity to infection [1]
The common theme is that bacteria must be motile to colonize the host but must become non-motile to chronically persist; this has been observed in many pathogenic bacteria including species of Vibrio and Pseudomonas
We show that step-wise loss of flagellar motility confers a proportional ability to evade phagocytic engulfment, independent of the flagellum itself acting as a phagocytic activator
Summary
Pathogen recognition by the innate immune system is one of the first lines of defense in cellular immunity to infection [1]. With the use of flagellated and non-flagellated swimming-defective P. aeruginosa genetic mutants, we demonstrated that it is not the loss of the flagellum itself, but rather the loss of flagellar-based swimming motility that allows P. aeruginosa to avoid phagocytic clearance [4]. It is currently unclear how the loss of bacterial swimming motility enables phagocytic evasion from innate immune cells and, to date, no published reports have examined in detail the dynamics of non-opsonized P. aeruginosaphagocyte association and subsequent fate as a function of bacterial swimming motility
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