Engulfment and destruction of invading microorganisms by phagocytosis are critical components of the innate immune response. In addition, phagocytosis is also required for the clearance of apoptotic bodies, an essential aspect of tissue homeostasis and remodeling. Here, we summarize the current knowledge of the cellular and molecular basis of phagosome formation and maturation. We discuss the manner in which phagocytosis is subverted by certain pathogens and consider congenital disorders that affect phagocyte function.

Analysis of luminal lysosomal pH in combination with heterologous expression of lysosomal-associated proteins indicates that peripheral lysosomes are more alkaline than juxtanuclear ones and that depletion of Rab7 and its effector, RILP, are associated with and can account for the reduced acidification.

αMβ2 integrin (complement receptor 3) is a major receptor for phagocytosis in macrophages. In other contexts, integrins' activities and functions are mechanically linked to actin dynamics through focal adhesions (FAs). We asked whether mechanical coupling of αMβ2 integrin to the actin cytoskeleton mediates phagocytosis. We found that particle internalization was driven by formation of Arp2/3 and formin-dependent actin protrusions that wrapped around the particle. Focal complex-like adhesions formed in the phagocytic cup that contained β2 integrins, FA proteins and tyrosine kinases. Perturbation of talin and Syk demonstrated that a talin-dependent link between integrin and actin and Syk-mediated recruitment of vinculin enable force transmission to target particles and promote phagocytosis. Altering target mechanical properties demonstrated more efficient phagocytosis of stiffer targets. Thus, macrophages use tyrosine kinase signaling to build a mechanosensitive, talin-and vinculin-mediated, FA-like molecular clutch, which couples integrins to cytoskeletal forces to drive particle engulfment.

In Salmonella enterica serovar Typhimurium, the stationary-phase sigma factor S (RpoS) is required for virulence, stress resistance, biofilm formation, and development of the rdar morphotype. This morphotype is a multicellular behavior characterized by expression of the adhesive extracellular matrix components cellulose and curli fimbriae. The Crl protein of Escherichia coli interacts with S and activates expression of Sregulated genes, such as the csgBAC operon encoding the subunit of the curli proteins, by an unknown mechanism. Here, we showed using in vivo and in vitro experiments that the Crl protein of Salmonella serovar Typhimurium is required for development of a typical rdar morphotype and for maximal expression of the csgD, csgB, adrA, and bcsA genes, which are involved in curli and cellulose biosynthesis. In vitro transcription assays and potassium permanganate reactivity experiments with purified His 6 -Crl showed that Crl directly activated S -dependent transcription initiation at the csgD and adrA promoters. We observed no effect of Crl on 70 -dependent transcription. Crl protein levels increased during the late exponential and stationary growth phases in Luria-Beratani medium without NaCl at 28°C. We obtained complementation of the crl mutation by increasing S levels. This suggests that Crl has a major physiological impact at low concentrations of S .