Flagella-driven bacterial motility, referred to as swimming, has been recognized for over 20 years to affect the ability of bacteria to infect and colonize a host. 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. Therefore it makes sense that the immune system would evolve mechanisms to exploit this virulence determinant of pathogenic bacteria. This paper presents evidence that flagellar motility is recognized by innate immune cells as a phagocytic activation signal. It shows 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. This is not due to motility- co-regulated secretions or compensatory genetic changes by the bacteria, but instead is due to a mechano-sensory response whereby phagocytic cells respond directly to flagellar motility. This represents a novel mechanism by which the innate immune system facilitates clearance of bacterial pathogens, and provides an explanation for how selective pressure may result in bacteria with down-regulated flagellar gene expression and motility as is observed in isolates taken from chronic infections.
Step-Wise Loss of Bacterial Flagellar Torsion Confers Progressive Phagocytic Evasion. (2011) PLoS Pathog 7(9): e1002253. doi:10.1371/journal.ppat.1002253
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.